Health Articles
AHA Scientific Statement
2009 Focused Updates: ACC/AHA Guidelines for the
Management of Patients With ST-Elevation Myocardial
Infarction (Updating the 2004 Guideline and 2007 Focused
Update) and ACC/AHA/SCAI Guidelines on Percutaneous
Coronary Intervention (Updating the 2005 Guideline and 2007
A Report of the American College of Cardiology Foundation/American
Heart Association Task Force on Practice Guidelines
Frederick G. Kushner, MD, FACC, FAHA, FSCAI, Co-Chair; Mary Hand, MSPH, RN, FAHA, Co-Chair*;
Sidney C. Smith, Jr, MD, FACC, FAHA, Chair; Spencer B. King III, MD, MACC, FSCAI, Co-Chair;
Jeffrey L. Anderson, MD, FACC, FAHA; Elliott M. Antman, MD, FACC, FAHA;
Steven R. Bailey, MD, FACC, FSCAI; Eric R. Bates, MD, FACC, FAHA;
James C. Blankenship, MD, FACC, FSCAI; Donald E. Casey, Jr, MD, MPH, MBA;
Lee A. Green, MD, MPH; Judith S. Hochman, MD, FACC, FAHA;
Alice K. Jacobs, MD, FACC, FAHA, FSCAI; Harlan M. Krumholz, MD, SM, FACC, FAHA;
Douglass A. Morrison, MD, PhD, FACC, FSCAI; Joseph P. Ornato, MD, FACC, FAHA;
David L. Pearle, MD, FACC, FAHA; Eric D. Peterson, MD, MPH, FACC, FAHA;
Michael A. Sloan, MD, MS, FACC, FAHA; Patrick L. Whitlow, MD, FACC, FAHA;
David O. Williams, MD, FACC, FAHA, FSCAI
*The opinions expressed in this article should not be construed as necessarily representing an official position of the US Department of Health and Human Services,
the Agency for Healthcare Research and Quality, or the US Government, by whom M. Hand is employed.
†Recused from Section 3, Thienopyridines; Section 4, Parenteral Anticoagulants; Section 5, Triage and Transfer for PCI.
‡Recused from Section 3, Thienopyridines; Section 4, Parenteral Anticoagulants.
§Recused from Section 6, Intensive Glucose Control.
储Recused from Section 2, Glycoprotein IIb/IIIa Receptor Antagonists; Section 3, Thienopyridines.
¶Recused from Section 3, Thienopyridines.
#Recused from Section 3, Thienopyridines; Section 7, Thrombus Aspiration; Section 8, Use of Stents; Section 11, PCI for Left Main Coronary Artery Disease.
**Recused from Section 3, Thienopyridines.
††Society for Cardiovascular Angiography and Interventions Representative.
‡‡Recused from Section 10, Fractional Flow Reserve.
§§Recused from Section 3, Thienopyridines; Section 5, Triage and Transfer for PCI; Section 8, Use of Stents.
储储Former Task Force member during this writing effort.
This document was approved by the American College of Cardiology Foundation Board of Trustees in September 2009, by the American Heart Association
Science Advisory and Coordinating Committee in September 2009, and by the Society for Cardiovascular Angiography and Interventions Board of Trustees in October2009.
The American Heart Association requests that this document be cited as follows: Kushner FG, Hand M, Smith SC Jr, King SB 3rd, Anderson JL,
Antman EM, Bailey SR, Bates ER, Blankenship JC, Casey DJ Jr, Green LA, Hochman JS, Jacobs AK, Krumholz HM, Morrison DA, Ornato JP, PearleDL, Peterson ED, Sloan MA, Whitlow PL, Williams DO. 2009 Focused updates: ACC/AHA guidelines for the management of patients with ST-elevationmyocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention(updating the 2005 guideline and 2007 focused update): a report of the American College of Cardiology Foundation/American Heart Association TaskForce on Practice Guidelines. Circulation. 2009;120:2271–2306.
This article has been copublished in the Journal of the American College of Cardiology and Catheterization and Cardiovascular Interventions.
Copies: This document is available on the World Wide Web sites of the American College of Cardiology (www.acc.org), the American Heart
Association (my.americanheart.org), and the Society for Cardiovascular Angiography and Interventions (scai.org). A copy of the document is alsoavailable at http://www.americanheart.org/presenter.jhtml?identifier⫽3003999 by selecting either the "topic list" link or the "chronological list" link (No.
KJ-0734). To purchase additional reprints, call 843-216-2533 or e-mail [email protected].
Expert peer review of AHA Scientific Statements is conducted at the AHA National Center. For more on AHA statements and guidelines development,
Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express
permission of the American Heart Association. Instructions for obtaining permission are located at http://www.americanheart.org/presenter.jhtml?identifier⫽4431. A link to the "Permission Request Form" appears on the right side of the page.
(Circulation. 2009;120:2271-2306.)
2009 American College of Cardiology Foundation and American Heart Association, Inc.
Circulation is available at http://circ.ahajournals.org
December 1, 2009
STEMI WRITING GROUP MEMBERS
Frederick G. Kushner, MD, FACC, FAHA, FSCAI, Co-Chair; Mary Hand, MSPH, RN, FAHA, Co-Chair*;
Elliott M. Antman, MD, FACC, FAHA†; Eric R. Bates, MD, FACC, FAHA‡;
Donald E. Casey, Jr, MD, MPH, MBA; Lee A. Green, MD, MPH§;
Judith S. Hochman, MD, FACC, FAHA储; Harlan M. Krumholz, MD, SM, FACC, FAHA;
Joseph P. Ornato, MD, FACC, FAHA¶; David L. Pearle, MD, FACC, FAHA;
Michael A. Sloan, MD, MS, FACC, FAHA; Sidney C. Smith, Jr, MD, FACC, FAHA
PCI WRITING GROUP MEMBERS
Sidney C. Smith, Jr, MD, FACC, FAHA, Chair; Spencer B. King III, MD, MACC, FSCAI, Co-Chair#;
Jeffrey L. Anderson, MD, FACC, FAHA**; Steven R. Bailey, MD, FACC, FSCAI††‡‡;
James C. Blankenship, MD, FACC, FSCAI††; Alice K. Jacobs, MD, FACC, FAHA, FSCAI§§;
Douglass A. Morrison, MD, PhD, FACC, FSCAI††; Eric D. Peterson, MD, MPH, FACC, FAHA**;
Patrick L. Whitlow, MD, FACC, FAHA; David O. Williams, MD, FACC, FAHA, FSCAI**
ACCF/AHA TASK FORCE MEMBERS
Alice K. Jacobs, MD, FACC, FAHA, Chair 2009 –2011; Sidney C. Smith, Jr, MD, FACC, FAHA,
Immediate Past Chair 2006 –2008储储; Jeffrey L. Anderson, MD, FACC, FAHA, Vice Chair;
Christopher E. Buller, MD, FACC; Mark A. Creager, MD, FACC, FAHA;
Steven M. Ettinger, MD, FACC; Robert A. Guyton, MD, FACC, FAHA;
Jonathan L. Halperin, MD, FACC, FAHA; Harlan M. Krumholz, MD, SM, FACC, FAHA储储;
Frederick G. Kushner, MD, FACC, FAHA; Rick Nishimura, MD, FACC, FAHA储储;
Richard L. Page, MD, FACC, FAHA储储; Lynn G. Tarkington, RN;
William G. Stevenson, MD, FACC, FAHA; Clyde W. Yancy, MD, FACC, FAHA
Table of Contents
8. Recommendations for the Use of Stents in STEMI . 2288
8.1. Stent Selection for STEMI . . . . . .2288
2009 STEMI and PCI Focused Updates . . . . .2273
PCI Focused Update Section . . . . . . . .2289
9. Recommendation for Angiography in Patients
1. Introduction . . . . . . . . . . .2274
With Chronic Kidney Disease . . . . . . 2289
1.1. Methodology and Evidence Review . . . 2274
9.1. Angiography in Patients With Chronic
1.2. Organization of Committee and Relationships
Kidney Disease. . . . . . . . . 2289
With Industry and Other Entities. . . . 2275
10. Recommendations for Use of Fractional
1.3. Document Review and Approval. . . . 2275
Flow Reserve. . . . . . . . . . .2289
STEMI and PCI Focused Update Section . . . . 2276
10.1. Fractional Flow Reserve. . . . . . 2289
2. Recommendations for the Use of
11. Recommendations for PCI for Unprotected
Glycoprotein IIb/IIIa Receptor Antagonists. . .2276
Left Main Coronary Artery Disease. . . . .2290
2.1. Glycoprotein IIb/IIIa Receptor Antagonists . 2276
11.1. Unprotected Left Main Coronary
3. Recommendations for the Use of Thienopyridines . 2277
Artery Disease . . . . . . . . .2290
3.1. Thienopyridines . . . . . . . . .2277
12. Recommendations for the Timing of Angiography
3.1.1. Additional Thienopyridine Information . 2280
and Antiplatelet Therapy in UA/NSTEMI . . .2292
3.1.2. Choice of Thienopyridine for PCI
12.1. Timing of Angiography . . . . . . 2292
12.2. Timing of GP IIb/IIIa Receptor Antagonist
3.2. Proton Pump Inhibitors and
Therapy in UA/NSTEMI Patients
Dual-Antiplatelet Therapy for ACS . . . 2281
Undergoing Angiography . . . . . .2292
4. Recommendations for the Use of
Appendix 1. Author Relationships With Industry and
Parenteral Anticoagulants . . . . . . . 2282
Other Entities—ST-Elevation Myocardial
4.1. Parenteral Anticoagulants. . . . . . 2282
Infarction . . . . . . . . .2294
5. Recommendations for Triage and Transfer for PCI . .2283
Appendix 2. Author Relationships With Industry and
5.1. Triage and Transfer for PCI . . . . . 2283
Other Entities—Percutaneous Coronary
5.1.1. STEMI Patients Who Are Candidates
Intervention . . . . . . . . . 2295
for Reperfusion . . . . . . .2283
Appendix 3. Reviewer Relationships With Industry
6. Recommendations for Intensive Glucose
and Other Entities—2009 STEMI and
PCI Focused Updates . . . . . .2296
6.1. Intensive Glucose Control . . . . . .2286
Appendix 4. Dosing Table for Antiplatelet and Anticoagulant
7. Recommendation for Thrombus Aspiration
Therapy Discussed in This Focused
During PCI for STEMI . . . . . . . .2287
Update to Support PCI in STEMI . . . 2299
7.1. Thrombus Aspiration . . . . . . . 2287
Appendix 5. Triage and Transfer for PCI . . . .2301
Kushner et al
2009 Focused Updates: STEMI and PCI Guidelines
Appendix 6. Outcomes of PCI Versus CABG for
size of the treatment effect and an estimate of the certainty of
Unprotected Left Main Coronary
the treatment effect. Note that a recommendation with level
Artery Disease . . . . . . . . 2301
of evidence B or C does not imply that the recommendation
is weak. Many important clinical questions addressed inguidelines do not lend themselves to clinical trials. Although
2009 STEMI and PCI Focused Updates
randomized trials may not be available, there may be a very
clear clinical consensus that a particular test or therapy is
A primary challenge in the development of clinical practice
useful and effective. Both the classification of recommenda-
guidelines is keeping pace with the stream of new data on
tions and level of evidence listed in the focused updates are
which recommendations are based. In an effort to respond
based on consideration of the evidence reviewed in previous
promptly to new evidence, the American College of Cardi-
iterations of the guideline and the focused update. Of note,
ology Foundation/American Heart Association (ACCF/AHA)
the implications of older studies that have informed recom-
Task Force on Practice Guidelines has created a "focused
mendations but have not been repeated in contemporary
update" process to revise the existing guideline recommen-
settings are considered carefully.
dations that are affected by evolving data or opinion. Before
The ACCF/AHA practice guidelines address patient popula-
the initiation of this focused approach, periodic updates and
tions (and healthcare providers) residing in North America. As
revisions of existing guidelines required up to 3 years to
such, drugs that are not currently available in North America are
complete. Now, however, new evidence will be reviewed in
discussed in the text without a specific class of recommendation.
an ongoing fashion to more efficiently respond to important
For studies performed in large numbers of subjects outside of
science and treatment trends that could have a major impact
North America, each writing group reviews the potential impact
on patient outcomes and quality of care. Evidence will be
of different practice patterns and patient populations on the
reviewed at least twice a year, and updates will be initiated on
treatment effect and on the relevance to the ACCF/AHA target
an as-needed basis as quickly as possible, while maintaining
population to determine whether the findings should inform a
the rigorous methodology that the ACCF and AHA have
developed during their 25 years of partnership.
The ACCF/AHA practice guidelines are intended to assist
These updated guideline recommendations reflect a con-
healthcare providers in clinical decision making by describ-
sensus of expert opinion after a thorough review primarily of
ing a range of generally acceptable approaches for the
late-breaking clinical trials identified through a broad-based
diagnosis, management, and prevention of specific diseases
vetting process as being important to the relevant patient
or conditions. The guidelines attempt to define practices that
population, as well as a review of other new data deemed to
meet the needs of most patients in most circumstances. The
have an impact on patient care (see Section 1.1, Methodology
ultimate judgment regarding care of a particular patient must
and Evidence Review, for details). This focused update is not
be made by the healthcare provider and patient in light of all
intended to represent an update based on a full literature
the circumstances presented by that patient. Thus, there are
review from the date of the previous guideline publication.
circumstances in which deviations from these guidelines may
Specific criteria/considerations for inclusion of new data
be appropriate. Clinical decision making should consider the
include the following:
quality and availability of expertise in the area where care isprovided. These guidelines may be used as the basis for
publication in a peer-reviewed journal;
regulatory or payer decisions, but the ultimate goals are
large randomized, placebo-controlled trial(s);
quality of care and serving the patient's best interests.
nonrandomized data deemed important on the basis of
Prescribed courses of treatment in accordance with these
results that affect current safety and efficacy assumptions;
recommendations are effective only if they are followed by
strength/weakness of research methodology and findings;
the patient. Because a lack of patient adherence may ad-
likelihood of additional studies influencing current findings;
versely affect treatment outcomes, healthcare providers
impact on current performance measure(s) and/or likeli-
should engage the patient in active participation with the
hood of need to develop new performance measure(s);
requests and requirements for review and update from the
The ACCF/AHA Task Force on Practice Guidelines makes
practice community, key stakeholders, and other sources
every effort to avoid actual, potential, or perceived conflicts
free of relationships with industry or other potential bias;
of interest that may arise as a result of industry relationships
number of previous trials showing consistent results; and
or personal interests among the writing committee. Specifi-
need for consistency with a new guideline or guideline revision.
cally, all members of the writing committee, as well asreviewers of the document, are asked to disclose all such
In analyzing the data and developing updated recommen-
relevant relationships pertaining to the trials and other evi-
dations and supporting text, the focused update writing group
dence under consideration (see Appendixes 1, 2, and 3). All
used evidence-based methodologies developed by the ACCF/
guideline recommendations require a confidential vote by the
AHA Task Force on Practice Guidelines, which are described
writing group and must be approved by a consensus of the
members voting. Members who recused themselves from
The schema for classification of recommendations and
voting are noted on the title page of this document. Members
level of evidence is summarized in Table 1, which also
must recuse themselves from voting on any recommendations
illustrates how the grading system provides an estimate of the
to which their relationships with industry and other entities
December 1, 2009
Applying Classification of Recommendations and Level of Evidence
*Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as gender, age, history of diabetes, history of prior
myocardial infarction, history of heart failure, and prior aspirin use. A recommendation with Level of Evidence B or C does not imply that the recommendation is weak.
Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Even though randomized trials are not available, there maybe a very clear clinical consensus that a particular test or therapy is useful or effective.
†In 2003, the ACCF/AHA Task Force on Practice Guidelines developed a list of suggested phrases to use when writing recommendations. All guideline
recommendations have been written in full sentences that express a complete thought, such that a recommendation, even if separated and presented apart fromthe rest of the document (including headings above sets of recommendations), would still convey the full intent of the recommendation. It is hoped that this willincrease readers' comprehension of the guidelines and will allow queries at the individual recommendation level.
apply. Writing group members who did not participate are not
focused update or the full-text guidelines are revised. This
listed as authors of this focused update. The work of the
focused update is published in the December 1, 2009, issues
writing group was supported exclusively by the ACCF and
of the Journal of the American College of Cardiology and
AHA without commercial support. Writing group members
Circulation as an update to the full-text guideline, and it is
volunteered their time for this effort.
also posted on the American College of Cardiology (ACC;
With the exception of the recommendations presented here,
www.acc.org), AHA (my.americanheart.org), and Society for
the full-text guidelines remain current.2,3 Only the recommen-
Cardiovascular Angiography and Interventions (SCAI;
dations from the affected section(s) of the full-text guidelines are
scai.org) World Wide Web sites.
included in this focused update. Recommendations from any
Alice K. Jacobs, MD, FACC, FAHA
section of a guideline affected by a change are presented with
Chair, ACCF/AHA Task Force on Practice Guidelines
notation as to whether they are new or have been modified;however, recommendations that remain unchanged in each
section are not included in this focused update. When evidenceaffects recommendations in more than 1 set of guidelines, those
1.1. Methodology and Evidence Review
guidelines are updated concurrently whenever possible.
Late-breaking clinical trials presented at the 2007 and 2008
The recommendations in this focused update will be
annual scientific meetings of the ACC, AHA, Transcatheter
considered current until they are superseded by another
Cardiovascular Therapeutics, the European Society of Cardi-
Kushner et al
2009 Focused Updates: STEMI and PCI Guidelines
ology, and the 2009 annual scientific sessions of the ACC
America. The writing group also notes that the AHA/ACCF
were reviewed by the standing guideline writing committee
and the Heart Rhythm Society have published updated
along with the parent Task Force and other experts to identify
recommendations for the standardization and interpretation of
those trials and other key data that may impact guideline
the electrocardiogram with a separate section on acute
recommendations. On the basis of the criteria/considerations
noted above, recent trial data and other clinical information were
To provide clinicians with a comprehensive set of data,
considered important enough to prompt a focused update of the
whenever possible, the exact event rates in various treatment
ACC/AHA 2004 Guidelines for the Management of Patients
arms of clinical trials are presented to permit calculation of
With ST-Elevation Myocardial Infarction and the ACC/AHA
the absolute risk difference and number needed to treat
2005 Guidelines for Percutaneous Coronary Intervention, inclu-
(NNT) or harm; the relative treatment effects are described
sive of their respective 2007 focused updates.2–5
either as odds ratio, relative risk (RR), or hazard ratio (HR)
The ST-elevation myocardial infarction (STEMI) and per-
depending on the format used in the original publication.
cutaneous coronary intervention (PCI) writing groups to-
Along with all other statistical point estimates, the confidence
gether considered the following studies: Two meta-analyses,
interval (CI) for those statistics are added when available.
"A Comparison of Abciximab and Small Molecule Glyco-
Consult the full-text or executive summary versions of the
protein IIb/IIIa Inhibitors in Patients Undergoing Primary
ACC/AHA 2004 Guidelines for the Management of Patients
Percutaneous Coronary Intervention,"6 and "Benefits From
With ST-Elevation Myocardial Infarction or the ACC/AHA/
Small Molecule Administration as Compared With Abcix-
SCAI 2005 Guidelines for Percutaneous Coronary Interven-
imab Among Patients With ST-Segment Elevation Myo-
tion, as well as their respective 2007 focused updates, for
cardial Infarction Treated With Primary Angioplasty,"7
policy on clinical areas not covered by the present focused
FINESSE (Facilitated PCI in Patients With ST-Elevation
update.2–5 Unchanged recommendations from previous itera-
Myocardial Infarction),8 the HORIZONS-AMI (Harmonizing
tions of the guidelines are not listed in this document and
Outcomes With Revascularization and Stents in Acute Myo-
remain current policy. Individual recommendations updated
cardial Infarction),9 BRAVE-3 (Bavarian Reperfusion Alter-
in this focused update will be incorporated into future
natives Evaluation-3),10 MULTISTRATEGY (Multicentre
revisions of the full-text guidelines.
Evaluation of Single High-Dose Bolus Tirofiban VersusAbciximab With Sirolimus-Eluting Stent or Bare Metal Stent
1.2. Organization of Committee and Relationships With
Industry and Other Entities
in Acute Myocardial Infarction Study),11 ON-TIME 2 (On-
For this focused update, all members of the 2004 STEMI
going Tirofiban in Myocardial Infarction Evaluation),12
guideline, 2007 STEMI focused update, 2005 PCI guideline,
TRITON-TIMI 38 (Trial to Assess Improvement in Thera-
and 2007 PCI focused update writing committees were
peutic Outcomes by Optimizing Platelet Inhibition With
invited to participate; those who agreed (referred to as the
Prasugrel–Thrombolysis in Myocardial Infarction),13
2009 Focused Update Writing Group) were required to
TRANSFER-AMI (Trial of Routine ANgioplasty and Stent-
disclose all relationships with industry and other entities
ing after Fibrinolysis to Enhance Reperfusion in Acute
relevant to the data under consideration. The policies used for
Myocardial Infarction),14 CARESS-in-AMI (Combined Ab-
relationships with industry were those in effect at the initial
ciximab Reteplase Stent Study in Acute Myocardial Infarc-
meeting of this committee, which included disclosure of
tion),15 NICE-SUGAR (Normoglycemia in Intensive Care
relationships 12 months prior to initiation and a chair with no
Evaluation—Survival Using Glucose Algorithm Regula-
relevant relationships except in a situation where more than
tion),16 TAPAS (Thrombus Aspiration during Percutaneous
one chair is named. In this circumstance, one chair will have
no relevant relationships and the other may have relation-
Study),17 and EXPIRA (Thrombectomy With Export Catheter
ships. Each recommendation required a confidential vote by
in Infarct-Related Artery During Primary Percutaneous Cor-
the writing group members before and after external review
onary Intervention).18 Additionally, the PCI writing group
of the document. Any writing group member with a relation-
considered the CARE (Cardiac Angiography in Renally
ship with industry relevant to the recommendation was
Impaired Patients),19 FAME (Fractional Flow Reserve versus
recused from voting on that recommendation. The PCI
Angiography for Multivessel Evaluation) study,20 SYNTAX
writing group included 2 representatives from SCAI.
(Synergy Between Percutaneous Intervention With Taxus andCardiac Surgery),21 Early ACS (Early versus Delayed, Pro-
1.3. Document Review and Approval
visional Eptifibatide in Acute Coronary Syndromes),22 and
This document was reviewed by 3 official reviewers nomi-
TIMACS (Timing of Intervention in Patients With Acute
nated by the ACCF and 4 official reviewers nominated by the
Coronary Syndromes) studies.23 When considering the new
AHA, 1 official reviewer nominated by the SCAI, 6 review-
data for this focused update, the writing group faced the task
ers from the ACCF Interventional Council, 2 reviewers from
of weighing evidence from studies that had enrolled large
the ACCF Imaging Council, and 22 content reviewers. All
numbers of subjects outside North America. Although noting
reviewer information on relationships with industry and other
that practice patterns and the rigor applied to data collection,
entities was collected and distributed to the writing commit-
as well as the genetic makeup of subjects, may influence the
tee and is published in Appendix 3. This document was
observed magnitude of a treatment's effect, the writing group
approved for publication by the governing bodies of the
believed the data were relevant to the formulation of recom-
ACCF, the AHA, and the SCAI (specifically, the PCI portion
mendations for management of STEMI and PCI in North
of the guideline).
December 1, 2009
Recommendations for the Use of Glycoprotein IIb/IIIa Receptor Antagonists
2004/2005/2007 Recommendations: 2004 STEMIGuideline Section 6.3.1.6.8.2.3; Also 2005 PCIGuideline Section 6.2.2
2009 Joint STEMI/PCI Focused Update Recommendations
Class IIa
1. It is reasonable to start treatment with abciximab
1. It is reasonable to start treatment with glycoprotein IIb/IIIa
Modified recommendation
as early as possible before primary PCI (with or
receptor antagonists (abciximab9,11 关Level of Evidence: A兴,
without stenting) in patients with STEMI. (Level of
tirofiban11,12 关Level of Evidence: B兴 or eptifibatide6,7,9 关Level of
Evidence: B)
Evidence: B兴) at the time of primary PCI (with or without stenting)
changed from IIb to IIa
in selected patients with STEMI.
for tirofiban andeptifibatide).
Class IIb
1. Treatment with tirofiban or eptifibatide may be
1. The usefulness of glycoprotein IIb/IIIa receptor antagonists (as part
Modified recommendation
considered before primary PCI (with or without
of a preparatory pharmacological strategy for patients with STEMI
(text modified; level of
stenting) in patients with STEMI. (Level of
before their arrival in the cardiac catheterization laboratory for
evidence changed from
Evidence: C)
angiography and PCI) is uncertain.8,10 (Level of Evidence: B)
STEMI and PCI Focused Update Section
receiving high-dose tirofiban (25 mcg/kg bolus followed by0.15 mcg/kg per min for 18 hours) at first medical contact
2. Recommendations for the Use of Glycoprotein
before transport for primary PCI were also treated with
IIb/IIIa Receptor Antagonists
unfractionated heparin (UFH; 5000 U), clopidogrel (600 mg),
(See Table 2 and Appendix 4.)
and ASA. Patients in the high-dose tirofiban group had
2.1. Glycoprotein IIb/IIIa Receptor Antagonists
improved ST-segment resolution (primary end point) before
In considering the use of intravenous glycoprotein (GP)
and 1 hour after PCI (P⫽0.003) compared with those receiv-
IIb/IIIa receptor antagonists for STEMI, the writing group
ing placebo (NNT⫽100). However, there was no significant
noted that much of the evidence favoring the use of these
difference in Thrombolysis In Myocardial Infarction (TIMI)
agents was established in the era before dual oral antiplatelet
grade 3 flow or blush grade and no significant difference in
therapy and largely by placebo-controlled comparisons. Con-
major bleeding or minor bleeding. There was no significant
temporary management of STEMI patients involves a com-
difference in death, recurrent MI, or urgent target-vessel
plex array of antithrombotics, including dual oral antiplatelet
revascularization (TVR) between the tirofiban and placebo
therapy (aspirin [acetylsalicylic acid; ASA] plus a thienopy-
groups at 30 days.25
ridine) and an anticoagulant. There is a paucity of trials
In the HORIZONS-AMI trial,9 patients undergoing pri-
adequately powered for assessment of clinical end points that
mary PCI for STEMI were randomized to treatment with
have reevaluated the current relative role of intravenous GP
UFH plus a GP IIb/IIIa receptor antagonist (abciximab or
IIb/IIIa receptor antagonists with respect to other pharmacolog-
double-bolus eptifibatide) or to bivalirudin alone with provi-
ical therapy in STEMI patients. Accordingly, a reevaluation of
sional IIb/IIIa. Aspirin and a thienopyridine were adminis-
the value of GP IIb/IIIa antagonists in STEMI is appropriate, but
tered before catheterization. (See the full discussion of the
the ability to draw definitive conclusions is limited.
trial under Section 4, Recommendations for the Use of
At least 3 trials evaluated GP IIb/IIIa antagonists as
Parenteral Anticoagulants.) Seven hundred fifty-seven of the
adjuncts to oral antiplatelet therapy in the setting of primary
1661 patients who received UFH received a double bolus of
PCI. The findings of these trials question whether GP IIb/IIIa
eptifibatide and infusion, whereas 53 of 1661 in the bivaliru-
antagonists provide significant additional benefit to STEMI
din arm received eptifibatide. At 30 days, rates of major
patients who have received dual-antiplatelet therapy before
bleeding and total adverse events were higher among patients
catheterization. In the BRAVE-3 study, 800 patients pres-
treated with GP IIb/IIIa antagonists and heparin than among
enting within 24 hours of a STEMI were pretreated with 600
those given bivalirudin alone.
mg of clopidogrel and then randomly assigned in a double-
Two meta-analyses of randomized trials were published
blind manner to receive either abciximab or placebo in the
that compared small-molecule GP IIb/IIIa antagonists with
intensive care unit before being sent for PCI.10 The primary
abciximab in STEMI patients undergoing primary PCI.6,7 In
end point was infarct size measured by single photon emis-
each case, there was no statistically significant difference in
sion computed tomography before hospital discharge. At 30
30-day mortality, reinfarction, or major TIMI bleeding, and
days, the composite of death, recurrent myocardial infarction
there was no significant difference in death or reinfarction at
(MI), stroke, or urgent revascularization of the infarct-related
8 months between groups. There was also no statistically
artery was not significantly different in the 2 groups (abcix-
significant difference in postprocedural TIMI flow grade 3 or
imab 5%, placebo 3.8%; 95% CI 0.7 to 2.6; P⫽0.4). There
ST-segment resolution. On the basis of these studies, the
was no significant difference in infarct size or major bleeding.
present writing group judged that the totality of evidence
ON-TIME 2 was a randomized, placebo-controlled, multi-
indicates that the various GP IIb/IIIa antagonists demonstrate
center European trial that included 491 patients receiving
similar effectiveness in the setting of primary PCI.
high-dose tirofiban and 493 receiving placebo within a
MULTISTRATEGY was an open-label, multicenter, ran-
median of 76 minutes from onset of symptoms.12 Patients
domized European trial with a 2-by-2 factorial design that
Kushner et al
2009 Focused Updates: STEMI and PCI Guidelines
randomized 745 STEMI patients undergoing primary PCI to
high-dose bolus tirofiban versus abciximab infusion and
Since the publication of the last guidelines,4,5 evidence has
sirolimus-eluting stent versus bare-metal stent (BMS).11 The
emerged about prasugrel, a thienopyridine that achieves
prespecified primary end points were the achievement of 50%
greater inhibition of platelet aggregation than clopidogrel.27
resolution of ST-segment elevation at 90 minutes after PCI,
The pivotal trial for prasugrel, TRITON-TIMI 38, focused on
powered for noninferiority, and the rate of major adverse
patients with ACS who were referred for PCI.
cardiac events (MACE) at 8 months, powered for superiority.
TRITON-TIMI 38 randomly assigned 13 608 patients with
All patients received ASA at the usual doses, clopidogrel 300
moderate- to high-risk ACS, 3534 of whom had STEMI, to
mg orally then 75 mg per day, and UFH. There was a similar
receive prasugrel (6813 patients received a 60-mg loading
rate of at least 50% ST-segment resolution at 90 minutes after
dose and a 10-mg daily maintenance dose) or clopidogrel
primary PCI with abciximab and tirofiban (RR 1.020; 97.5%
(6795 patients received a 300-mg loading dose and a 75-mg
CI 0.958 to 1.086; P⫽0.001 for noninferiority). Rates of
daily maintenance dose) for an average follow-up of 14.5
MACE, including all-cause death, clinical reinfarction, or
months. Aspirin was prescribed within 24 hours of PCI.
TVR, and hemorrhagic (major and minor bleeding) compli-
Clinical end points were assessed at 30 and 90 days and then
cations were similar. The incidence of severe or moderate
every 3 to 15 months.27
thrombocytopenia was more common with abciximab than
Prasugrel was associated with a significant 2.2% absolute
with tirofiban (4.0% versus 0.8%, P⫽0.004).
reduction and a 19% relative reduction in the primary
In an analysis of the predictors of stent thrombosis after
efficacy end point, a composite of the rate of death due to
primary PCI in acute MI presented at the 2009 ACC Scien-
cardiovascular causes (including arrhythmia, congestive heart
tific Sessions, titled "Predictors of Stent Thrombosis After
failure, shock, and sudden or unwitnessed death), nonfatal
Primary Angioplasty in Acute Myocardial Infarction: The
MI, or nonfatal stroke during the follow-up period. The
HORIZONS-AMI Trial,"69 there was no significant differ-
primary efficacy end point occurred in 9.9% of patients
ence in the 1-year rate of stent thrombosis with the heparin
receiving prasugrel and 12.1% of patients receiving clopi-
plus GP IIb/IIIa receptor antagonists compared with eptifi-
dogrel (HR for prasugrel versus clopidogrel 0.81; 95% CI
batide and abciximab (3.6% versus 2.8%, P⫽0.93), which
0.73 to 0.90; P⬍0.001). A significant reduction in the
suggests that eptifibatide has the same impact as abciximab
primary end point was seen in the prasugrel group by the first
on stent thrombosis incidence.
prespecified time point, which was 3 days (4.7% in the
One investigation, FINESSE, addressed the issue of timing
prasugrel group versus 5.6% in the clopidogrel group; HR
of GP IIb/IIIa antagonist administration. This double-blind,
0.82; 95% CI 0.71 to 0.96; P⫽0.01), and persisted throughout
randomized, placebo-controlled study of 2453 patients with
the follow-up period. From Day 3 to the end of the study, the
STEMI explored the use of pre-PCI treatment with a half-
primary end point had occurred in 5.6% of patients receiving
dose fibrinolytic agent plus abciximab, pre-PCI abciximab
prasugrel and in 6.9% of patients receiving clopidogrel (HR
alone, and abciximab at the time of PCI.8 The primary end
0.80; 95% CI 0.70 to 0.93; P⫽0.003). Prasugrel decreased
point was the composite of death due to all causes, ventricular
cardiovascular death, MI, and stroke by 138 events
fibrillation that occurred more than 48 hours after random-
(NNT⫽46).27 The rate of MI with subsequent death due to
ization, cardiogenic shock, and congestive heart failure dur-
cardiovascular causes was also reduced in the prasugrel group
ing the first 90 days after randomization. The results of the
(P⫽0.02). The difference in the primary end point was
trial are discussed in Section 5.1, Triage and Transfer for PCI.
largely related to the difference in rates of nonfatal MI (7.3%
This trial showed no benefit (and a tendency toward excess
for prasugrel versus 9.5% for clopidogrel; HR 0.76; 95% CI
bleeding) with prehospital abciximab compared with abcix-
0.67 to 0.85; P⬍0.001). There were no significant differences
imab at the time of PCI. The writing group concluded there
in the 2 treatment groups in the rates of stroke or of death due
was no benefit of administration of abciximab before primary
to cardiovascular causes not preceded by recurrent MI (at 15
PCI, alone or in combination with reteplase. On the basis of
months, the nonfatal stroke rate was 1.0% for both prasugrel
this trial and ON-TIME 2, the writing group concluded thatthe use of GP IIb/IIIa antagonists before primary PCI is of
and clopidogrel; HR for prasugrel⫽1.02; CI 0.71 to 1.45;
uncertain benefit.
P⫽0.93; the rate of deaths due to cardiovascular causes not
Given the results of the studies cited above, the writing
preceded by recurrent MI was 2.1% for prasugrel versus 2.4%
group concluded that in the setting of dual-antiplatelet ther-
for clopidogrel; HR 0.89; CI 0.70 to 1.12; P⫽0.31). There
apy with UFH or bivalirudin as the anticoagulant, current
were significant reductions in the rates of ischemic events in
evidence indicates that adjunctive use of a GP IIb/IIIa
the prasugrel group compared with the clopidogrel group:
antagonist can be useful at the time of primary PCI but cannot
Rates of MI were 7.4% for prasugrel versus 9.7% for
be recommended as routine therapy. These agents might
clopidogrel (P⬍0.001); urgent TVR rates were 2.5% for
provide more benefit in selective use, for example, for the
prasugrel versus 3.7% for clopidogrel (P⬍0.001); and rates
patient with a large thrombus burden or for patients who have
of stent thrombosis were 1.1% for prasugrel versus 2.4% for
not received adequate thienopyridine loading.
clopidogrel (HR 0.48; 95% CI 0.36 to 0.64; P⬍0.001).
Prasugrel was associated with a significant increase in the
3. Recommendations for the Use of
rate of bleeding, notably, TIMI major hemorrhage, which was
observed in 2.4% of patients taking prasugrel and in 1.8% of
(See Table 3 and Appendix 4.)
patients taking clopidogrel (HR for prasugrel versus clopidogrel
December 1, 2009
Recommendations for the Use of Thienopyridines
Comments (All Modified
Recommendations Are for
STEMI Recommendations
PCI Recommendations
2009 Joint STEMI/PCI Focused Update Recommendations
Patients With ACS)
2004 STEMI Guidelines,
2007 PCI Update, Table 14
4. For patients who have undergone
4. A loading dose of clopidogrel,* generally
1. A loading dose of thienopyridine is recommended for STEMI patients for
Modified recommendation
diagnostic cardiac catheterization
600 mg, should be administered before
whom PCI is planned. Regimens should be 1 of the following:
(changed text).
and for whom PCI is planned,
or when PCI is performed. (Level of
a. At least 300 to 600 mg of clopidogrel† should be given as early as
clopidogrel should be started and
Evidence: C) In patients undergoing PCI
possible before or at the time of primary or nonprimary PCI. (Level of
continued for at least 1 month
within 12 to 24 hours of receiving
Evidence: C)
after bare metal stent
fibrinolytic therapy, a clopidogrel oral
b. Prasugrel 60 mg should be given as soon as possible for primary
implantation and for several
loading dose of 300 mg may be
PCI.26,27 (Level of Evidence: B)
months after drug-eluting stent
considered. (Level of Evidence: C)
c. For STEMI patients undergoing nonprimary PCI, the following
implantation (3 months for
regimens are recommended:
sirolimus, 6 months for
(i) If the patient has received fibrinolytic therapy and has been given
paclitaxel) and for up to 12
clopidogrel, clopidogrel should be continued as the thienopyridine
months in patients who are not
of choice (Level of Evidence: C);
at high risk for bleeding. (Level
(ii) If the patient has received fibrinolytic therapy without a
of Evidence: B)
thienopyridine, a loading dose of 300 to 600 mg‡ of clopidogrel
should be given as the thienopyridine of choice (Level of
Evidence: C);
(iii) If the patient did not receive fibrinolytic therapy, either a loading
dose of 300 to 600 mg of clopidogrel should be given or, once
the coronary anatomy is known and PCI is planned, a loading
dose of 60 mg of prasugrel should be given promptly and no
later than 1 hour after the PCI.26,27 (Level of Evidence: B)
5. For all post-PCI stented patients receiving
2. The duration of thienopyridine therapy should be as follows:
Modified recommendation
a DES, clopidogrel 75 mg daily should be
a. In patients receiving a stent (BMS or drug-eluting stent [DES]) during
(pertains to STEMI and
given for at least 12 months if patients
PCI for ACS, clopidogrel 75 mg daily†27–29 (Level of Evidence: B) or
are not at high risk of bleeding. For
prasugrel 10 mg daily§27 (Level of Evidence: B) should be given for
post-PCI patients receiving a BMS,
at least 12 months;
关NSTEMI兴 based on
clopidogrel should be given for a
b. If the risk of morbidity because of bleeding outweighs the anticipated
TRITON-TIMI 38).
minimum of 1 month and ideally up to
benefit afforded by thienopyridine therapy, earlier discontinuation
12 months (unless the patient is at
should be considered. (Level of Evidence: C)
increased risk of bleeding; then it should
be given for a minimum of 2 weeks).
(Level of Evidence: B)
2007 STEMI Update, Section 9
2. In patients taking clopidogrel in
3. In patients taking a thienopyridine in whom CABG is planned and can
Modified recommendation
whom CABG is planned, the drug
be delayed, it is recommended that the drug be discontinued to allow
(added prasugrel).
should be withheld for at least 5
for dissipation of the antiplatelet effect. (Level of Evidence: C) The
days and preferably for 7 days
period of withdrawal should be at least 5 days in patients receiving
unless the urgency for
clopidogrel2,30 (Level of Evidence: B) and at least 7 days in patients
revascularization outweighs the
receiving prasugrel†27 (Level of Evidence: C), unless the need for
risks of excess bleeding. (Level
revascularization and/or the net benefit of the thienopyridine outweighs
of Evidence: B)
the potential risks of excess bleeding.31 (Level of Evidence: C)
Class IIa
2004 STEMI Guidelines, Section
2007 PCI Update, Table 14
1. If clopidogrel is given at the time of
Deleted recommendation
procedure, supplementation with GP
IIb/IIIa receptor antagonists can be
beneficial. (Level of Evidence: B)
2. For patients with an absolute
Deleted recommendation
contraindication to aspirin, it is
reasonable to give a 300-mg to 600-mg
loading dose of clopidogrel, administered
at least 6 hours before PCI, and/or GP
IIb/IIIa antagonists, administered at the
time of PCI. (Level of Evidence: C)
Class IIb
2004 STEMI Guidelines, Section
2007 PCI Update, Table 14
1. Continuation of clopidogrel therapy
1. Continuation of clopidogrel or prasugrel§ beyond 15 months may be
Modified recommendation
beyond 1 year may be considered in
considered in patients undergoing DES placement.27 (Level of Evidence: C)
(changed text).
patients undergoing DES placement.
(Level of Evidence: C)
Kushner et al
2009 Focused Updates: STEMI and PCI Guidelines
Comments (All Modified
Recommendations Are for
STEMI Recommendations
PCI Recommendations
2009 Joint STEMI/PCI Focused Update Recommendations
Patients With ACS)
Class III
1. In STEMI patients with a prior history of stroke and transient ischemic
New recommendation
attack for whom primary PCI is planned, prasugrel is not recommended
as part of a dual-antiplatelet therapy regimen. (Level of Evidence: C)
*Available data for prasugrel use are for PCI for acute coronary syndrome (ACS) and not elective PCI. Recommendations for elective PCI with clopidogrel use are
not being updated in this guideline focused update.
†The optimum loading dose of clopidogrel has not been established. Randomized trials establishing its efficacy and providing data on bleeding risks used a loading
dose of 300 mg orally followed by a daily oral dose of 75 mg.26,27 Higher oral loading doses such as 600 mg or more than 900 mg36 of clopidogrel more rapidly inhibitplatelet aggregation and achieve a higher absolute level of inhibition of platelet aggregation, but the additive clinical efficacy and safety of higher oral loading doseshave not been rigorously established. The necessity for giving a loading dose of clopidogrel before PCI is driven by the pharmacokinetics of clopidogrel, for whichseveral hours are required to achieve desired levels of platelet inhibition. For post-PCI patients receiving a stent (BMS or DES), a daily maintenance dose should begiven for at least 12 months and for up to 15 months unless the risk of bleeding outweighs the anticipated net benefit afforded by a thienopyridine.
‡Clopidogrel loading dose after fibrinolytic therapy: For patients given fibrin- and non–fibrin-specific fibrinolytic drugs who are undergoing PCI within 24 hours, 300
mg; for patients given a fibrin-specific fibrinolytic undergoing PCI after more than 24 hours, 300 to 600 mg; for patients given a non–fibrin-specific fibrinolyticundergoing PCI between 24 and 48 hours, 300 mg; for patients given a non–fibrin-specific fibrinolytic undergoing PCI after 48 hours, 300 to 600 mg.
§Patients weighing ⬍60 kg have an increased exposure to the active metabolite of prasugrel and an increased risk of bleeding on a 10-mg once-daily maintenance
dose. Consideration should be given to lowering the maintenance dose to 5 mg in patients who weigh ⬍60 kg. The effectiveness and safety of the 5-mg dose havenot been studied prospectively. For post-PCI patients receiving a stent (BMS or DES), a daily maintenance dose should be given for at least 12 months and for upto 15 months unless the risk of bleeding outweighs the anticipated net benefit afforded by a thienopyridine. Do not use prasugrel in patients with active pathologicalbleeding or a history of transient ischemic attack or stroke. In patients ⱖ75 years of age, prasugrel is generally not recommended because of the increased risk offatal and intracranial bleeding and uncertain benefit, except in high-risk situations (patients with diabetes or a history of prior MI) in which its effect appears to begreater and its use may be considered. Do not start prasugrel in patients likely to undergo urgent CABG. When possible, discontinue prasugrel at least 7 days beforeany surgery. Additional risk factors for bleeding include body weight ⬍60 kg, propensity to bleed, and concomitant use of medications that increase the risk of bleeding(eg, warfarin, heparin, fibrinolytic therapy, or chronic use of nonsteroidal anti-inflammatory drugs).
1.32; 95% CI 1.03 to 1.68, P⫽0.03), which represented an
A post hoc analysis suggested there were 3 subgroups of
increase in the relative rate of major bleeding of 32%. From the
ACS patients who did not have a favorable net clinical benefit
standpoint of safety, prasugrel was associated with an in-
(defined as the rate of death due to any cause, nonfatal MI,
crease of 35 TIMI major and non– coronary artery bypass
nonfatal stroke, or non–CABG-related nonfatal TIMI major
graft bleeds (number needed to harm⫽167).27 Also, greater
bleeding) from the use of prasugrel or who had net harm:
rates of life-threatening bleeding were evident in the prasug-
Patients with a history of stroke or transient ischemic attack
rel group than in the clopidogrel group: 1.4% versus 0.9%,
(TIA) before enrollment had net harm from prasugrel (HR
respectively (HR for prasugrel 1.52; 95% CI 1.08 to 2.13;
1.54; 95% CI 1.02 to 2.32; P⫽0.04), patients 75 years of age
P⫽0.01), which included nonfatal bleeding (1.1% versus
and older had no net benefit from prasugrel (HR 0.99; 95% CI
0.9%; HR for prasugrel 1.25; 95% CI 0.87 to 1.81;
0.81 to 1.21; P⫽0.92); and patients with a body weight of less
P⫽0.23) and fatal bleeding (0.4% versus 0.1%; HR for
than 60 kg had no net benefit from prasugrel (HR 1.03; 95%
prasugrel 4.19; 95% CI 1.58 to 11.11; P⫽0.002). In the
CI 0.69 to 1.53; P⫽0.89). In both treatment groups, patients
few patients who underwent coronary artery bypass graft
with at least 1 of these risk factors had higher rates of
(CABG), TIMI major bleeding through 15 months was also
bleeding than those without them.27 A pharmacokinetic anal-
greater with prasugrel than with clopidogrel (13.4% versus
ysis showed greater exposure to the active metabolite of
3.2%, respectively; HR for prasugrel 4.73; 95% CI 1.90 to
prasugrel for patients who weighed less than 60 kg and who
11.82; P⬍0.001).27 Despite the increase in bleeding, the
were 75 years old or older.38
net clinical-benefit end point, which included all-cause
The US Food and Drug Administration (FDA) approved
mortality, ischemic events, and major bleeding events,
prasugrel in July 2009 and incorporated the aforementioned
favored prasugrel.27
subgroup findings into its labeling by citing a contraindica-
Prasugrel showed superior efficacy in major prespecified
tion against prasugrel use in patients with a history of TIA or
subgroups in the overall ACS population. The benefit tended to
stroke and active pathological bleeding. The FDA further
be greater among the 3146 patients with diabetes (12.2% of
recommends that consideration be given to lowering the
whom had the primary end point in the prasugrel group versus
maintenance dose of prasugrel to 5 mg in patients who weigh
17.0% in the clopidogrel group; HR 0.70; 95% CI 0.58 to 0.85;
less than 60 kg, with a note that the effectiveness and safety
P⬍0.001) than among the 10 462 patients without diabetes
of the 5-mg dose have not been studied prospectively to date.
(9.2% of whom had the primary end point in the prasugrel group
The FDA labeling information includes a general warning
versus 10.6% in the clopidogrel group; HR 0.86; 95% CI 0.76 to
against the use of prasugrel in patients older than 75 years of
0.98; P⫽0.02). The rate of definite or probable stent thrombosis
age because of concerns of an increased risk of fatal and
was significantly reduced in the prasugrel group compared with
intracranial bleeding and uncertain benefit, except in high-
the clopidogrel group, as noted.27
risk situations (patients with diabetes or a history of prior
December 1, 2009
MI), in which case its effect appears to be greater and its use
Determination of patient groups that should be considered
may be considered.37
for continuation of dual-antiplatelet treatment beyond 12
In focusing specifically on patients with STEMI, the
months is based on patient-level factors (eg, age, history of
primary composite end point of cardiovascular death, nonfa-
bleeding) and lesion characteristics (eg, bifurcation, small-
tal MI, or nonfatal stroke was significantly reduced in patients
diameter vessel).28
assigned to prasugrel at 30 days compared with patients who
In previous studies of patients with prior stroke or TIA, use
received clopidogrel (6.5% versus 9.5%; HR 0.68; 95% CI
of dual-antiplatelet therapy has been associated with an
0.54 to 0.87; P⫽0.0017), and this trend persisted to 15
increased risk of adverse outcomes, notably intracranial
months (HR 0.79; 95% CI 0.65 to 0.97; P⫽0.0221).13
bleeding, compared with single-antiplatelet therapy. In the
Furthermore, in the STEMI group, the key secondary end
MATCH (Management of Atherothrombosis With Clopi-
point of cardiovascular death, MI, or urgent TVR was
dogrel in High-Risk Patients With TIA or Stroke) trial40 in
significantly reduced with prasugrel at 30 days (P⫽0.0205)
which patients with prior stroke or TIA and additional risk
and 15 months (P⫽0.0250).13 At 30 days and 15 months, the
factors (n⫽7599) were allocated to clopidogrel 75 mg or
individual end points of cardiovascular death and MI, as well
combination therapy with clopidogrel 75 mg plus ASA 75 mg
as stent thrombosis, were reduced with prasugrel.13
per day, there was no significant benefit of combination
The interaction testing for efficacy and safety showed no
therapy compared with clopidogrel alone in reducing the
significant difference in bleeding risk regardless of the type
primary outcome of the composite of ischemic stroke, MI,
of ACS (eg, UA/NSTEMI versus STEMI). Thus, the STEMI
vascular death, or rehospitalization due to ischemic events, or
results for efficacy and safety are consistent with the main
any of the secondary outcomes. The risk of major hemorrhage
results of the trial. In a post hoc analysis of patients with
was significantly increased in the combination-therapy group
anterior MI, event rates at 15 months for the primary end
compared with those given clopidogrel alone, with a 1.3%
point were lower with prasugrel (9.8% for prasugrel versus
absolute increase in life-threatening bleeding. Although clo-
16.3% for clopidogrel; HR 0.57; 95% CI 0.42 to 0.78;
pidogrel plus ASA is recommended over ASA alone for
P⫽0.0003). In patients with nonanterior MI, treatment effects
patients with ACS,41–43 the results of MATCH do not suggest
did not differ for the primary end point (10.1% for prasugrel
a similar risk-benefit ratio for stroke and TIA survivors. The
versus 9.9% for clopidogrel; HR 1.02; 95% CI 0.78 to 1.34;
AHA/American Stroke Association's Guidelines for Preven-
P⫽0.8749). The test for heterogeneity of the effect of
tion of Stroke in Patients With Ischemic Stroke or Transient
prasugrel was significant (P⫽0.0053), which suggests that
Ischemic Stroke contain a Class III recommendation for the
the benefit might vary by the location of the MI. Data were
use of ASA in combination with clopidogrel in patients with
consistent in both the primary and secondary PCI
prior stroke or TIA.44 On the other hand, a post hoc analysis
from the CHARISMA (Clopidogrel for High Atherothrom-
The writing group weighed the current data regarding the
botic Risk and Ischemic Stabilization, Management, and
use of thienopyridine therapy in patients who remain hospi-
Avoidance) trial, which included 9478 patients, suggested
talized after STEMI and are candidates for CABG and
that patients with documented prior MI, ischemic stroke, or
retained the 2007 focused update recommendation of empiric
symptomatic peripheral artery disease derive benefit from
discontinuation of clopidogrel therapy for at least 5 days and
dual-antiplatelet therapy with clopidogrel plus ASA.45 Al-
at least 7 days in patients receiving prasugrel before planned
though MATCH and CHARISMA did not involve STEMI
patients, the writing group recommended weighing the ben-
Platelet function testing to determine the degree of platelet
efits and risks of prescribing clopidogrel and ASA in patients
with a recent history of TIA or stroke. Given prasugrel's
39 may be used, and if platelet function has normalized,
CABG may be performed at an earlier time. Additionally, other
greater tendency to cause intensive inhibition of plateletaggregation in general and the findings of increased levels of
strategies of platelet inhibition (GP IIb/IIIa receptor antagonists)
bleeding compared with clopidogrel in this population, the
may be used if recurrent ischemia is a concern during the waiting
use of prasugrel as part of a dual-antiplatelet therapy regimen
period for CABG. Ultimately, the patient's clinical status will
in patients with prior stroke or TIA is contraindicated.37
determine the risk-to-benefit ratio of CABG compared withawaiting restoration of platelet function.
3.1.1. Additional Thienopyridine Information
The results of TRITON-TIMI 38 influenced dosing recom-
Although clopidogrel in combination with ASA has been
mendations for loading and chronic thienopyridine therapy
shown to reduce recurrent coronary events in the posthospi-
with prasugrel. Sixty milligrams of prasugrel is now recom-
talized ACS population,32,43,46 the response to clopidogrel
mended as a loading dose for primary PCI in STEMI. For
varies among patients, and clopidogrel resistance has been
secondary PCI in those patients who have recurrent ischemia
observed.43 Information is accumulating about the variations
or other reasons for planned intervention during their course
in the antiplatelet effect of clopidogrel in patients with
of treatment, 60 mg of prasugrel may be given after the
loss-of-function alleles in the gene encoding CYP450
coronary anatomy has been identified (to avoid dosing those
2C19.32,46–50 These patients form a subgroup in which failure
patients who require CABG) either before, during, or within
of clopidogrel effectiveness has been linked to adverse
1 hour of PCI.27 Furthermore, 10 mg of prasugrel may be
clinical outcomes.30,47–51 In TRITON-TIMI 38 and 3 of the
used in addition to ASA for chronic dual-antiplatelet
cohort studies,47,49,52 patients who were carriers of a reduced-
function CYP450 2C19 allele had significantly lower levels
Kushner et al
2009 Focused Updates: STEMI and PCI Guidelines
of the active metabolite of clopidogrel, diminished platelet
MIs, with deaths and nonfatal strokes being similar, bleeding
inhibition, and increased rates of cardiovascular events (eg,
was increased in the prasugrel group.27 In addition, the
death, MI, stroke), including stent thrombosis,53 compared
comparison of the 2 drugs is based on a single large trial.
with the extensive metabolizers.54 In another cohort study
Also, the loading dose of clopidogrel in TRITON-TIMI 38
with 2208 patients,50 the increased event rate was observed
was lower than is currently recommended in these guidelines.
only in poor metabolizers. (Prasugrel has a higher level of
Furthermore, there are some emerging studies that suggest
inhibition of platelet aggregation than clopidogrel and a more
there may be some patients who are resistant to clopidogrel,
rapid onset of action.55 Its metabolism is not affected by the
but there is little information about the use of strategies to
2C19 allele variant.56)
select patients who might do better with prasugrel. There is
Accordingly, the effective clopidogrel dose for an individ-
not yet experience with the use of prasugrel in routine
ual undergoing PCI for STEMI may not be known. A large
community practice. As a result, the writing group believes
randomized trial57 is attempting to determine whether adjust-
that there is some uncertainty regarding the net benefit and
ment of clopidogrel therapy on the basis of platelet function
risks of 1 drug over another for a given patient. Consider-
testing with a point-of-care assay safely improves outcomes
ations of efficacy in the prevention of thrombosis and risk of
after PCI with DES. As noted in the drug dosing table
an adverse effect related to bleeding, as well as experience
(Appendix 4), the current recommended loading dose for
with a given medication, may best guide decisions about the
clopidogrel is uncertain. In addition, a period of several hours
choice of thienopyridine for individual patients.
is required to metabolize clopidogrel to its active metabolite,
3.2. Proton Pump Inhibitors and Dual-Antiplatelet
which leaves a window of time during which there is a
Therapy for ACS
reduced level of effectiveness even in responders.
Proton pump inhibitors (PPIs) are often prescribed prophy-
With regard to clopidogrel loading for PCI after a patient
lactically when clopidogrel is started, to prevent gastrointes-
has received fibrinolytic therapy, there are no studies that
tinal complications such as ulceration and related bleeding59
have formally tested a 600-mg (or higher) clopidogrel loading
due to dual-antiplatelet therapy, in particular ASA and
dose administered with fibrinolytic treatment. The only study
clopidogrel.32 Coupled with concern about the gastrointesti-
that tested any clopidogrel dose with a fibrinolytic was the
nal precautions, there has been increased emphasis on the
CLARITY-TIMI 28 (Clopidogrel as Adjunctive Reperfusion
prevention of premature discontinuation of dual-antiplatelet
Therapy–Thrombolysis in Myocardial Infarction 28) study,
therapy, particularly in patients who have received a stent
which randomized 3491 patients 75 years of age and younger
(BMS or DES), for whom 12 months of antiplatelet therapy is
who were receiving fibrinolytic therapy within 12 hours of
recommended.28 PPI medications* have been found to inter-
STEMI to clopidogrel (300-mg oral loading dose; 75-mg oral
fere with the metabolism of clopidogrel.34
daily maintenance dose) or placebo.58 As described in the
Although there are studies that show a pharmacodynamic
2007 STEMI focused update,4 patients who received clopi-
interaction on ex vivo platelet function testing, to date there are
dogrel had a reduced rate of an occluded infarct artery,
no convincing randomized clinical trial data for an important
accomplished by preventing infarct-related reocclusion rather
clinical drug– drug interaction. Retrospective claims-based re-
than by facilitating early reperfusion.
ports suggesting clinical harm, some detailed below, may be
When considering a loading dose of clopidogrel for PCI after
confounded by different baseline characteristics and lack of
a patient has received a fibrinolytic agent, the available level of
compliance data. There have been retrospective reports of
evidence is limited (Level of Evidence: C), and consensus
adverse cardiovascular outcomes (eg, readmission for ACS)
opinion suggests it is dependent on how many hours have
when the antiplatelet regimen of clopidogrel and ASA is
elapsed since fibrinolytic therapy was administered before PCI.
accompanied by PPIs, assessed as a group, compared with the
For patients who have received any fibrinolytic agent and
use of this regimen without a PPI.32–34,60 In a retrospective
subsequently proceed to PCI within 24 hours, a dose of 300 mg
cohort study from the Veterans Affairs' medical records and
of clopidogrel as a loading dose is suggested. If the patient
pharmacy database, concomitant clopidogrel and PPI therapy
received a fibrin-specific fibrinolytic agent and then proceeds to
(with omeprazole, rabeprazole, lansoprazole, or pantoprazole) at
PCI after 24 hours has elapsed, a loading dose of 300 to 600 mg
any time point during follow-up of 8205 patients discharged for
may be considered. If at least 48 hours has elapsed after
ACS was associated with an increased risk of death or rehospi-
treatment with a non–fibrin-specific fibrinolytic agent, a dose of
talization for ACS.32 Other post hoc study analyses50,61 and a
300 to 600 mg may be considered.
retrospective data analysis from the NHLBI Dynamic Registry62
Prasugrel has not been studied in patients who have
in which PPIs were assessed as a class in combination with a
received fibrinolytic therapy. Thus, for STEMI patients un-
clopidogrel and an ASA regimen have not found an effect of PPI
dergoing nonprimary PCI who received prior fibrinolytic
therapy on the clinical effect of clopidogrel in ACS patients,
therapy without a thienopyridine, only a loading dose with
clopidogrel should be given as the thienopyridine of choice.
Some studies have suggested that adverse cardiovascular
3.1.2. Choice of Thienopyridine for PCI in STEMI
outcomes with the combination of clopidogrel and a PPI are
The guidelines do not endorse explicitly one of the thienopy-ridines over the other. There were several reasons for this
*PPIs include omeprazole, lansoprazole, pantoprazole, rabeprazole, and es-
decision. Although the composite efficacy end point favored
omeprazole (which are all available by prescription). Omeprazole is also sold
prasugrel, driven predominantly by a difference in nonfatal
over the counter for frequent heartburn.66
December 1, 2009
explained by the individual PPI, in particular the use of a PPI
was 6%.67 The writing committee concluded that additional
that inhibits CYP450 2C19, which includes omeprazole,
data, notably randomized controlled clinical trial data that
lansoprazole, and rabeprazole. The PPI omeprazole notably
have been peer reviewed and published, are needed before an
has been reported to significantly decrease the inhibitory
official recommendation can be made about the use of dual
effect of clopidogrel on platelet aggregation.63,64 One study
antiplatelet therapy with PPIs in the setting of ACS.
reported that the PPI pantoprazole was not associated withrecurrent MI among patients receiving clopidogrel, possibly
4. Recommendations for the Use of
because of its lack of inhibition of CYP450 2C19.33
Other studies have examined the thienopyridine agent
(See Table 4 and Appendix 4.)
prescribed with the PPI. One open-label drug study evaluated
4.1. Parenteral Anticoagulants
the effects of the PPI lansoprazole on the pharmacokinetics
Parenteral anticoagulants include intravenous UFH, bivaliru-
and pharmacodynamics of prasugrel and clopidogrel in
din, enoxaparin, and fondaparinux. Bivalirudin was briefly
healthy subjects given single doses of prasugrel (60 mg) and
cited in the 2007 STEMI focused update. The HORIZONS-
clopidogrel (300 mg) with and without concurrent lansopra-
AMI trial, which was reported subsequently, was a prospec-
zole 30 mg per day. The data suggest that inhibition of
tive, open-label, randomized, multicenter, international trial
platelet aggregation was reduced in patients who took the
that included 3602 patients with STEMI undergoing primary
combination of clopidogrel and lansoprazole, whereas it was
PCI. Patients were randomized to treatment with UFH plus a
unaffected after a prasugrel dose.56
GP IIb/IIIa receptor antagonist or to bivalirudin alone (with
Another study35 assessed the association of PPIs with the
provisional abciximab or double-bolus eptifibatide). The
pharmacodynamics and clinical efficacy of clopidogrel and
primary efficacy end point was a composite of net adverse
prasugrel, based on populations from 2 randomized trials, the
clinical events, including major bleeding plus MACE, a
PRINCIPLE (Prasugrel In Comparison to Clopidogrel for
composite of cardiovascular death, reinfarction, TVR for
Inhibition of Platelet Activation and Aggregation) TIMI-44
ischemia, and stroke within 30 days. Bivalirudin alone
trial65 and the TRITON-TIMI 38 trial.27 The findings indi-cated that first, PPI treatment attenuated the pharmacody-
resulted in a lower incidence of net adverse clinical events at
namic effects of clopidpgrel and, to a lesser extent, those of
30 days (9.2% versus 12.1%; RR 0.76; 95% CI 0.63 to 0.92;
prasugrel. Secondly, PPI treatment did not affect the clinical
P⫽0.005; NNT⫽34) and at 1 year (15.7% versus 18.3%, HR
outcome of patients given clopidogrel or prasugrel. This
0.84; 95% CI 0.71 to 0.98; P⫽0.3).9 The difference was
finding was true for all PPIs that were studied, including
driven by a significant decrease in major bleeding complica-
omeprazole and pantoprazole.
tions with bivalirudin at 30 days (4.9% versus 8.3%,
The FDA communication concerning an ongoing safety
P⫽0.001; number needed to harm⫽33) and 1 year (5.8%
review of clopidogrel bisulfate66 advises that healthcare
versus 9.2%, P⫽0.001). There was a statistically significant
providers avoid the use of clopidogrel in patients with
1% increase in stent thrombosis (n⫽17) within the first 24
impaired CYP2C19 function due to known genetic varia-
hours with bivalirudin but no subsequent difference (1.3%
tion or due to drugs that inhibit CYP2C19 activity. The
versus 0.3%, P⬍0.001). More deaths at 30 days occurred
FDA notes that there is no evidence that other drugs that
after major bleeding (n⫽26) than after reinfarction (n⫽10) or
reduce stomach acid, such as H2 blockers or antacids,
definite stent thrombosis (n⫽5).9 Treatment with bivalirudin
interfere with the antiplatelet activity of clopidogrel.
resulted in significantly lower 30-day rates of death due to
Further research with thienopyridines and PPI combina-
cardiac causes (1.8% versus 2.9%; RR 0.62; 95% CI 0.40 to
tions, particularly drugs that are not dependent on CYP450
0.95; P⫽0.03) and death due to all causes (2.1% versus 3.1%;
2C19, is needed. Consideration may be given to the use of H2
RR 0.66; 95% CI 0.44 to 1.00; P⫽0.047 compared with UFH
antagonists as an alternative to PPIs in the setting of dual-
plus GP IIb/IIIa inhibitors). At 1 year, MACE rates were
antiplatelet therapy, although they cannot be relied on to
identical, but there was a decrease in all-cause mortality with
protect as well as PPIs, and there are few data about their use
bivalirudin (3.4% versus 4.8%, P⫽0.03).68
with ASA.59 The FAMOUS (Famotidine for the Prevention of
Concerns about the trial include its open-label design and
Peptic Ulcers in Users of Low-Dose Aspirin) trial, a phase II,
the administration of UFH before randomization in 66% of
double-blind, randomized, placebo-controlled trial, found that
patients in the bivalirudin arm and 76% of patients in the
among patients with a history of coronary heart disease,
UFH plus GP IIb/IIIa receptor antagonist arm. Only 615
diabetes mellitus, or cerebrovascular disease who were taking
patients received bivalirudin monotherapy, and only 60% of
low-dose ASA, 12 weeks of famotidine 20 mg twice daily
patients in the trial received a 600-mg clopidogrel loading
(n⫽204) compared with placebo twice daily (n⫽200) was
dose. Major bleeding as defined in the publication included
beneficial in reducing the incidence of peptic ulcer or
hematomas of 5 cm, intracranial hemorrhage, and bleeding
esophagitis during follow-up endoscopy at 12 weeks. The rate
that required surgery. Additionally, the study put forth a
of occurrence of a gastric ulcer at endoscopy at 12 weeks was
composite primary end point that combined efficacy and
3.4% in the famotidine group versus 15% in the placebo
safety. Although there were no statistically significant inter-
group (P⫽0.0002), duodenal ulcer occurred in 0.5% versus
actions at 30 days between the treatment assignment and
8.5% (P⫽0.0045), and erosive esophagitis was seen in 4.4%
preprocedural UFH use or clopidogrel loading dose with
versus 19% (P⬍0.0001), respectively. Of note, in the famo-
respect to MACE or major bleeding, the occurrence of an
tidine group, clopidogrel use was 19% and dipyridamole use
increase in early stent thrombosis with bivalirudin and the
Kushner et al
2009 Focused Updates: STEMI and PCI Guidelines
Recommendations for the Use of Parenteral Anticoagulants
2009 Joint STEMI/PCI Focused Update
STEMI Recommendations
PCI Recommendations
2007 STEMI Update, Section 8
2007 PCI Guideline Update, Table 13
2. For patients undergoing PCI after having
1. For patients undergoing PCI after having received
1. For patients proceeding to primary
Modified recommendation. (Bivalirudin
received an anticoagulant regimen, the
an anticoagulant regimen, the following dosing
PCI who have been treated with
was added as an acceptable
following dosing recommendations should
recommendations should be followed:
ASA and a thienopyridine,
anticoagulant for primary PCI; text
a. For prior treatment with UFH, administer
recommended supportive
about UFH was modified to
a. For prior treatment with UFH,
additional boluses of UFH as needed to support
anticoagulant regimens include the
mention activated clotting time
administer additional boluses of UFH
the procedure, taking into account whether GP
levels. Information on enoxaparin
as needed to support the procedure,
IIb/IIIa receptor antagonists have been
a. For prior treatment with UFH,
and fondaparinux was not
taking into account whether GP IIb/IIIa
administered. (Level of Evidence: C) Bivalirudin
additional boluses of UFH should
receptor antagonists have been
may also be used in patients treated previously
be administered as needed to
administered. (Level of Evidence: C)
with UFH. (Level of Evidence: C)
maintain therapeutic activated
these drugs were unchanged.)
Bivalirudin may also be used in
b. For prior treatment with enoxaparin, if the last
clotting time levels, taking into
patients treated previously with UFH.
subcutaneous dose was administered at least 8
account whether GP IIb/IIIa
(Level of Evidence: C)
to 12 hours earlier, an IV (intravenous) dose of
receptor antagonists have been
b. For prior treatment with enoxaparin, if
0.3 mg/kg of enoxaparin should be given; if the
administered. (Level of
the last subcutaneous dose was
last subcutaneous dose was administered within
Evidence: C)
administered within the prior 8 hours,
the prior 8 hours, no additional enoxaparin
b. Bivalirudin is useful as a
no additional enoxaparin should be
should be given. (Level of Evidence: B)
supportive measure for primary
given; if the last subcutaneous dose
c. For prior treatment with fondaparinux, administer
PCI with or without prior treatment
was administered at least 8 to 12
additional intravenous treatment with an
with UFH.9 (Level of
hours earlier, an intravenous dose of
anticoagulant possessing anti-IIa activity, taking
Evidence: B)
0.3 mg per kg of enoxaparin should
into account whether GP IIb/IIIa receptor
be given. (Level of Evidence: B)
antagonists have been administered. (Level of
c. For prior treatment with fondaparinux,
Evidence: C)
administer additional intravenous
treatment with an anticoagulant
possessing anti-IIa activity taking into
account whether GP IIb/IIIa receptor
antagonists have been administered.
(Level of Evidence: C)
Class IIa
1. In STEMI patients undergoing PCI
New recommendation
who are at high risk of bleeding,
bivalirudin anticoagulation is
reasonable.9 (Level of Evidence: B)
excess bleeding with UFH and GP IIb/IIIa inhibitors may be
PCI.4 These terms are no longer used for the recommenda-
related to the degree of platelet inhibition and antithrombin
tions in this update so that the contemporary therapeutic
activity associated with these treatment doses.
choices that lead to reperfusion as part of the treatment of
A preliminary report suggested that the use of bivalirudin
patients presenting with STEMI can be described without
alone (P⫽0.005) and a lower loading dose of clopidogrel
these potentially misleading labels.
(300 versus 600 mg; P⫽0.01) were independent predictors of
A brief review of facilitated PCI, however, is needed. This
acute and subacute stent thrombosis rates, respectively.69
strategy involves full- or half-dose fibrinolytic therapy with
Probability values for secondary end points may not have
or without a GP IIb/IIIa receptor antagonist, followed by
been adjusted for multiple looks.
immediate PCI. Two studies addressed this issue: ASSENT-4
Therefore, the writing group now considers bivalirudin
PCI (Assessment of the Safety and Efficacy of a New
useful for primary PCI in STEMI whether or not the patient
Treatment Strategy With Percutaneous Coronary Interven-
received pretreatment with UFH. The risk of acute stent
tion),70 which was described in detail in the 2007 PCI and
thrombosis associated with bivalirudin appeared to be miti-
STEMI focused updates, and FINESSE,71 which was a
gated by the prior use of UFH and the risk of subacute stent
randomized, double-blind clinical trial of 2452 patients ran-
thrombosis by the use of a 600-mg loading dose of clopi-
domized within 6 hours of symptom onset to receive reduced-
dogrel. These data should be confirmed by prospective
dose reteplase plus abciximab followed by PCI (combination-
facilitated PCI), abciximab alone followed by PCI
5. Recommendations for Triage and Transfer
(abciximab-facilitated PCI), or placebo (primary PCI).
ASSENT-4 patients treated with fibrinolytic therapy
(See Table 5 and Appendix 5.)
before PCI had increased rates of adverse outcomes,including in-hospital death (6% versus 3%). The investi-
5.1. Triage and Transfer for PCI
gators theorized that suboptimal antithrombotic therapy
5.1.1. STEMI Patients Who Are Candidates for Reperfusion
(ie, the lack of a heparin infusion after bolus administra-
The 2007 STEMI Focused Update describes several strate-
tion, no upfront loading dose of clopidogrel, and prohibi-
gies for reperfusion, among them facilitated PCI and rescue
tion of IIb/IIIa use except for bailout) and a short time
December 1, 2009
Recommendations for Triage and Transfer for PCI
2009 Joint STEMI/PCI Focused Update Recommendations
1. Each community should develop a STEMI system of care that follows
New recommendation
standards at least as stringent as those developed for the AHA'snational initiative, Mission: Lifeline, to include the following:
ongoing multidisciplinary team meetings that include emergency
medical services, non–PCI-capable hospitals/STEMI referralcenters, and PCI-capable hospitals/STEMI receiving centers toevaluate outcomes and quality improvement data;
a process for prehospital identification and activation;
destination protocols for STEMI receiving centers;
transfer protocols for patients who arrive at STEMI referral centers
who are primary PCI candidates, are ineligible for fibrinolyticdrugs, and/or are in cardiogenic shock. (Level of Evidence: C)
Class IIa
1. It is reasonable for high-risk* patients who receive fibrinolytic
New recommendation
therapy as primary reperfusion therapy at a non–PCI-capable facility
to be transferred as soon as possible to a PCI-capable facility wherePCI can be performed either when needed or as a pharmacoinvasivestrategy. Consideration should be given to initiating a preparatoryantithrombotic (anticoagulant plus antiplatelet) regimen before andduring patient transfer to the catheterization laboratory.14,15 (Level ofEvidence: B)
Class IIb
(From 2007 STEMI Update, Section 5)
1. Facilitated PCI using regimens other than full-dose
1. Patients who are not at high risk who receive fibrinolytic therapy as
fibrinolytic therapy might be considered as a
primary reperfusion therapy at a non–PCI-capable facility may be
reperfusion strategy when all of the following are
considered for transfer as soon as possible to a PCI-capable facility
(changed text).
present: a. Patients are at high risk, b. PCI is not
where PCI can be performed either when needed or as a
immediately available within 90 minutes, and c.
pharmacoinvasive strategy. Consideration should be given to
Bleeding risk is low (younger age, absence of
initiating a preparatory antithrombotic (anticoagulant plus antiplatelet)
poorly controlled hypertension, normal body
regimen before and during patient transfer to the catheterization
weight). (Level of Evidence: C)
laboratory. (Level of Evidence: C)
(From 2007 STEMI Update, Section 6)
1. A strategy of coronary angiography with intent to
Deleted recommendation
perform PCI in the absence of 1 or more of the
above Class I or IIa indications might be
reasonable in moderate- and high-risk patients,
but its benefits and risks are not well established.
The benefits of rescue PCI are greater the earlierit is initiated after the onset of ischemicdiscomfort. (Level of Evidence: C)
*High risk was defined in the CARESS-in-AMI15 study as STEMI patients with ⱖ1 high-risk feature (extensive ST-segment elevation, new-onset left bundle-branch
block, previous MI, Killip class ⬎2, or left ventricular ejection fraction ⱕ35% for inferior MIs; anterior MI alone with ⱖ2 mm of ST elevation in ⱖ2 leads also qualifiedthe patient as being at high risk). It was defined in TRANSFER-AMI14 as ⱖ2 mm of ST-segment elevation in 2 anterior leads or ST elevation of at least 1 mm in inferiorleads with at least 1 of the following: systolic blood pressure ⬍100 mm Hg, heart rate ⬎100 bpm, Killip class II to III, ⱖ2 mm of ST-segment depression in the anteriorleads, or ⱖ1 mm of ST elevation in right-sided lead V4 indicative of right ventricular involvement.
from fibrinolytic therapy to PCI contributed in part to the
difference would be significant if the trial had been allowed
adverse clinical outcomes.
to continue to its planned completion.
FINESSE8 showed that neither PCI preceded by abciximab
The indications for rescue PCI have been defined by a
and reteplase nor PCI preceded by abciximab alone was
combination of clinical and electrocardiographic clues that an
superior to abciximab used at the time of PCI among patients
infarct artery has not reperfused. These are relief of pain and
presenting within 4 hours of medical contact. Neither the
resolution of ST-segment elevation. Although complete relief
primary end point (a composite of death due to all causes,
of pain and complete resolution of ST elevation are reason-
ventricular function more than 48 hours after randomization,
ably predictive of reperfusion after fibrinolytic therapy, this is
cardiogenic shock, and congestive heart failure during the
not a common occurrence. In the 2007 STEMI Focused
first 90 days after randomization) nor mortality was signifi-
Update, the writing committee held that at 90 minutes after
cantly different among the groups. Although the study was
initiation of fibrinolytic therapy, if there was less than 50%
terminated early because of recruitment challenges, there was
ST-segment resolution in the lead that showed the greatest
less than a 2% chance that the primary treatment group
degree of ST elevation at presentation, then fibrinolytic
Kushner et al
2009 Focused Updates: STEMI and PCI Guidelines
therapy had likely failed to reperfuse the patient.4 If the
who had at least 1 high-risk feature (greater than or equal to
judgment was made that fibrinolytic therapy had not resulted
2 mm of ST-segment elevation in 2 anterior leads, systolic
in reperfusion after 90 minutes, then PCI performed at that
blood pressure less than 100 mm Hg, heart rate higher than
time was labeled rescue PCI.
100 bpm, Killip class II to III, 2 mm or more of ST-segment
The 2007 STEMI Focused Update4 recommended rescue
depression in the anterior leads, or 1 mm or more of ST
PCI in the following cases: Fibrinolytic-treated STEMI pa-
elevation in right-sided lead V4 indicative of right ventricular
tients meeting high-risk criteria (ie, cardiogenic shock [less
involvement for inferior MIs; anterior MI alone with 2 mm or
than 75 years of age, Class I; 75 years of age or older, Class
more of ST-segment elevation in 2 or more leads also
IIa]); hemodynamic or electrical instability; persistent ische-
qualified) and who were treated with fibrinolytic therapy
mic symptoms; and for certain moderate- and high-risk
were randomized to a pharmacoinvasive strategy (immediate
patients who did not strictly meet the above criteria (Class
transfer for PCI within 6 hours of fibrinolytic therapy) or to
IIb). These recommendations were based on results of the
standard treatment after fibrinolytic therapy, which included
REACT (Rescue Angioplasty Versus Conservative Treat-
rescue PCI as required for ongoing chest pain and less than
ment of Repeat Thrombolysis) trial74 which showed a clear
50% resolution of ST elevation at 60 to 90 minutes or
benefit of rescue PCI (over repeated doses of fibrinolytics or
hemodynamic instability. Standard-treatment patients who
medical management) in moderate- to high-risk patients with
did not require rescue PCI remained at the initial hospital for
failed reperfusion, as well as a meta-analysis of 8 rescue PCI
at least 24 hours, and coronary angiography within the first 2
trials (including REACT).73–76 The 2007 focused update
weeks was encouraged.
acknowledged that the expected benefits of rescue PCI are
All patients received standard-dose tenecteplase, ASA, and
greater the earlier it is initiated after the onset of ischemic
either UFH or enoxaparin. Clopidogrel loading (300 mg for
patients 75 years of age or younger and 75 mg for those older
Two new trials have helped inform this update: The
than 75 years of age) was strongly encouraged in all study
CARESS-in-AMI trial and the TRANSFER-AMI trial.
patients. GP IIb/IIIa receptor antagonists were administered
CARESS-in-AMI15 studied 600 STEMI patients 75 years of
at the PCI-capable hospitals according to standard practice at
age or younger with at least 1 high-risk feature (extensive
the institution. The primary end point of the trial was the
ST-segment elevation, new-onset left bundle-branch block,
30-day composite of the first occurrence of death, reinfarc-
previous MI, Killip class greater than 2, or left ventricular
tion, recurrent ischemia, new or worsening heart failure, and
ejection fraction 35% or less) who were treated initially at
cardiogenic shock.
non-PCI hospitals with half-dose reteplase, abciximab, hep-
The median time to administration of tenecteplase from
arin, and ASA within 12 hours of symptom onset.3 All
onset of symptoms was approximately 2 hours in both groups,
patients were randomized to immediate transfer for PCI or to
whereas the median time from tenecteplase administration to
standard treatment with transfer for rescue PCI if needed. PCI
catheterization was 2.8 hours in the pharmacoinvasive group
was performed in 85.6% of patients in the immediate PCI
and 32.5 hours in the standard-treatment group. Coronary
group, and rescue PCI was performed in 30.3% of the
angiography was performed in 98.5% versus 88.7% and PCI
standard treatment/transfer for rescue PCI group. There was a
in 84.9% versus 67.4% of the pharmacoinvasive and
shorter median time from fibrinolytic therapy to transfer to a
standard-treatment groups, respectively.
PCI-capable center in the immediate versus the rescue PCI
The primary end point of the trial occurred in 11.0% of the
group (110 versus 180 minutes, P⬍0.0001). Antiplatelet
pharmacoinvasive group compared with 17.2% of the
therapy with ASA and clopidogrel was used less frequently in
standard-treatment group (RR 0.64; 95% CI 0.47 to 0.84;
the standard care/rescue arm than in the early intervention
P⫽0.004). Importantly, the incidence of TIMI major and
group. The primary outcome (composite of all-cause mortal-
minor bleeding and GUSTO (Global Use of Strategies to
ity, reinfarction, and refractory myocardial ischemia within
Open Occluded Coronary Arteries)77 moderate and severe
30 days of randomization) occurred significantly less often
bleeding was not different between groups, although there
(4.4% versus 10.7%, P⫽0.004) in the immediate PCI group
was a higher incidence of GUSTO mild bleeding in the
than in the standard care/rescue PCI group (NNT⫽17). There
pharmacoinvasive group (13.0% compared with 9.0% in the
were no significant differences in the rates of major bleeding
standard-treatment group, P⫽0.036). The authors concluded
at 30 days (3.4% versus 2.3%, P⫽0.47) or stroke (0.7%
that after treatment with fibrinolytic therapy in STEMI
versus 1.3%, P⫽0.50) between groups. These results suggest
patients presenting to hospitals without PCI capability, trans-
that high-risk STEMI patients treated at non-PCI hospitals
fer to a PCI center to undergo coronary angiography and PCI
with a preparatory pharmacological strategy of half-dose
should be initiated immediately without waiting to determine
fibrinolytic therapy, abciximab, heparin, and ASA have
whether reperfusion has occurred. These results lend further
improved outcomes when transferred immediately to a PCI
support to the routine, early transfer of high-risk, fibrinolytic-
facility rather than when medical therapy is continued with
treated patients to a PCI center for early PCI supported by
transfer for rescue PCI only if there is evidence of failed
contemporary antiplatelet and antithrombotic therapy.
On the basis of this evidence, a pathway has been sug-
The TRANSFER-AMI study14 further tested the pharma-
gested for the care of STEMI patients that has been divided
coinvasive strategy concept in high-risk STEMI patients.
into those patients presenting to a PCI-capable facility and
Accordingly, 1059 patients who presented to a non–PCI-
those presenting to a non–PCI-capable facility (Appendix 5).
capable hospital within 12 hours of symptom onset of STEMI
Those seen at a PCI-capable facility should be moved
December 1, 2009
expeditiously to the catheterization laboratory, with appropri-
facility in that community should have an agreed-upon plan
ate antithrombotic therapy for catheterization and PCI if
for how STEMI patients are to be treated. This includes
appropriate. There has been discussion about whether the
which hospitals should receive STEMI patients from emer-
recommended door-to-balloon time (or first medical contact–
gency medical services units capable of obtaining diagnostic
to-balloon time) should be greater than 90 minutes, with the
ECGs, management at the initial receiving hospital, and
recognition that in certain patients, the mortality advantage of
written criteria and agreements for expeditious transfer of
primary PCI compared with fibrinolytic therapy is maintained
patients from non–PCI-capable to PCI-capable facilities.82
with more prolonged door-to-balloon times.78 However, the
The development of regional systems of STEMI care is a
writing groups continue to believe that the focus should be on
matter of utmost importance.83,84 This includes encouraging
developing systems of care to increase the number of patients
the participation of key stakeholders in collaborative efforts
with timely access to primary PCI rather than extending the
to evaluate care using standardized performance and quality
acceptable window for door-to-balloon time.79 Moreover, in a
improvement measures, such as those endorsed by the ACC
study of 43 801 patients with STEMI undergoing primary
and the AHA for ACS.85 Standardized quality-of-care data
PCI within the National Cardiovascular Data Registry, any
registries designed to track and measure outcomes, compli-
delay in time to reperfusion after arrival at the hospital was
cations, and adherence to evidence-based processes of care
associated with a higher adjusted risk of in-hospital mortality
for ACS are also critical: programs such as the National
in a continuous, nonlinear fashion (30 minutes⫽3.0%, 60
Cardiovascular Data Registry ACTION Registry, the AHA's
minutes⫽3.5%, 90 minutes⫽4.3%, 120 minutes⫽5.6%, 150
"Get With The Guidelines" quality improvement program,
minutes⫽7.0%, and 180 minutes⫽8.4%; P⬍0.001).80 Rather
and those performance-measurement systems required by the
than accepting a 90-minute door-to-balloon benchmark for
Joint Commission and the Centers for Medicare and Medic-
primary PCI, these data suggest an as-soon-as-possible
aid Services.86–89 More recently, the AHA has promoted its
"Mission: Lifeline" initiative, which was developed to en-
Those patients presenting to a non–PCI-capable facility
courage closer cooperation and trust among prehospital emer-
should be triaged to fibrinolytic therapy or immediate transfer
gency services, and cardiac care professionals.90 The evalu-
for PCI. This decision will depend on multiple clinical
ation of STEMI care delivery across traditional care-delivery
observations that allow judgment of the mortality risk of the
boundaries with these tools and other resources is imperative
STEMI, the risk of fibrinolytic therapy, the duration of the
to identify systems problems and to enable the application of
symptoms when first seen, and the time required for transport
modern quality improvement methods, such as Six Sigma, to
to a PCI-capable facility.3 If primary PCI is chosen, the
make necessary improvements.70,91–93
patient will be transferred for PCI. If fibrinolytic therapy ischosen, the patient will receive the agent(s), and a judgment
6. Recommendations for Intensive Glucose Control
as to whether the patient is high risk or not will be made. If
high risk, the patient should receive appropriate antithrom-
botic therapy and be moved immediately to a PCI-capablefacility for diagnostic catheterization and consideration of
6.1. Intensive Glucose Control
PCI. If not high risk, the patient may be moved to a
As detailed in the 2004 STEMI guideline and the 2007
PCI-capable facility after receiving antithrombotic therapy or
UA/NSTEMI guideline revision, randomized trial evidence
may be observed in the initial facility.
supported the use of insulin infusion to control hyperglyce-
Patients best suited for transfer for PCI are those STEMI
mia.3,97 A recently published randomized clinical trial of
patients who present with high-risk features, those with high
intensive versus conventional glucose control in critically ill
bleeding risk from fibrinolytic therapy, and patients pres-
patients raised uncertainty regarding the optimal level to
enting late, that is, more than 4 hours after onset of symp-
target when achieving glucose control. NICE-SUGAR, a
toms. The decision to transfer is a judgment made after
large, international randomized trial (n⫽6104) of adults
consideration of the time required for transport and the
admitted to the intensive care unit with either medical or
capabilities of the receiving hospital.2,5 Patients best suited
surgical conditions, compared intensive glucose control (tar-
for fibrinolytic therapy are those who present early after
get glucose range 81 to 108 mg/dL) with conventional
symptom onset with low bleeding risk. After fibrinolytic
glucose control (to achieve a glucose level less than 180
therapy, if the patient is not at high risk, transfer to a
mg/dL, with reduction and discontinuation of insulin if the
PCI-capable facility may be considered, especially if symp-
blood glucose level dropped below 144 mg/dL).16 Time-
toms persist and failure to reperfuse is suspected.
weighted glucose levels achieved were 115⫾18 mg/dL in the
The duration of symptoms should continue to serve as a
intensive glucose control group versus 144⫾23 mg/dL in the
modulating factor in selecting a reperfusion strategy for
conventional glucose control group. The risk of death was
STEMI patients. Although patients at high risk (eg, those
increased at 90 days in the intensive glucose control group by
with congestive heart failure, shock, and contraindications to
2.6% (27.5% versus 24.9%; odds ratio 1.14; 95% CI 1.02 to
fibrinolytic therapy) are best served with timely PCI, "inor-
1.08; P⫽0.02; number needed to harm⫽38). The result
dinate delays between the time from symptom onset and
remained the same after adjustment for potential confounders.
effective reperfusion with PCI may prove deleterious, espe-
There were significantly more episodes of treatment-related
cially among the majority of STEMI patients at relatively low
hypoglycemia in the intensely managed group (6.8% versus
risk" (p 1299).81 Accordingly, each community and each
0.5%, P⫽0.001), although the contribution of hypoglycemia
Kushner et al
2009 Focused Updates: STEMI and PCI Guidelines
Recommendations for Intensive Glucose Control in STEMI
2004/2005/2007 Recommendations: 2004 STEMIGuidelines
2009 Joint STEMI/PCI Focused Update Recommendations
1. An insulin infusion to normalize blood glucose
Recommendation is no longer current.
is recommended for patients with STEMI and
See 2009 Class IIa
complicated courses. (Level of Evidence: B)
recommendation #1.
Class IIa
1. It is reasonable to use an insulin-based regimen to achieve
New recommendation
and maintain glucose levels less than 180 mg/dL whileavoiding hypoglycemia* for patients with STEMI with eithera complicated or uncomplicated course.16,94–96 (Level ofEvidence: B)
1. During the acute phase (first 24 to 48 hours)
Recommendation is no longer current.
of the management of STEMI in patients with
See 2009 Class IIa
hyperglycemia, it is reasonable to administer
recommendation #1.
an insulin infusion to normalize blood glucoseeven in patients with an uncomplicatedcourse. (Level of Evidence: B)
*There is uncertainty about the ideal target range for glucose necessary to achieve an optimal risk-benefit ratio.
to excess mortality is uncertain.94,98 Overall, the hospital
7.1. Thrombus Aspiration
course and proximate causes of death were similar in the 2
Since the publication of the last STEMI and PCI focused
groups. Excess deaths in the intensive-control group were
updates, 2 new trials of manual thrombus aspiration have been
predominantly due to cardiovascular causes (absolute differ-
published. TAPAS was a single-center, unblinded, randomized
ence 5.8%; P⫽0.02). More patients in the intensive-control
clinical trial that compared 2 catheter-based reperfusion strate-
group than in the conventional-control group were treated
gies in 1071 patients with STEMI.17,102 Before coronary angiog-
raphy, patients were randomized to manual thrombus aspiration
Because NICE-SUGAR enrolled critically ill medical and
before PCI (55.1% by direct stenting, 28.6% by balloon angio-
surgical patients, the degree to which its results can be
plasty followed by stenting, 10.1% by PCI without thrombus
extrapolated to the management of patients with STEMI is
aspiration) or conventional PCI with balloon angioplasty fol-
unclear. Although recent data from a small, mechanistic
lowed by stenting. BMS were implanted in 92% of PCI
clinical trial28,29,98 suggest that glucose control may reduce
procedures. All patients were treated with ASA, 600 mg of
inflammation and improve left ventricular ejection fraction in
clopidogrel, UFH, and abciximab unless contraindicated. TIMI
patients with acute myocardial infarction (AMI), whether it
myocardial blush grade 0 or 1 occurred in 17.1% of patients with
will improve patient outcomes remains uncertain.
thrombus aspiration and 26.3% of those with conventional PCI
A consensus statement by the American Association of
(P⬍0.001). Complete resolution of ST-segment elevation oc-
Clinical Endocrinologists and the American Diabetes Asso-
curred in 56.6% and 44.2%, respectively (P⬍0.001). Death,
ciation99 summarized that "although hyperglycemia is asso-
reinfarction, and TVR rates at 30 days were not significantly
ciated with adverse outcomes after AMI, reduction of glyce-
different (6.8% versus 9.4%).17 However, at 1 year, rates of
mia per se, and not necessarily the use of insulin, is associated
cardiac death (3.6% versus 6.7%, P⫽0.02) and cardiac death or
with improved outcomes. It remains unclear, however,
nonfatal reinfarction (5.6% versus 9.9%, P⫽0.009) were lower
whether hyperglycemia is a marker of underlying health
with thrombus aspiration. Low myocardial blush grade and
status or is a mediator of complications after AMI. Noniatro-
incomplete ST-segment resolution were associated with clinical
genic hypoglycemia has also been associated with adverseoutcomes and is a predictor of higher mortality" (p 1120).
There is a clear need for a well-designed, definitive random-
EXPIRA was a smaller (n⫽175) randomized clinical trial
ized trial of target-driven glucose control in STEMI that has
that also compared thrombus aspiration with conventional
meaningful clinical end points to determine glucose treatment
PCI, but only in patients with TIMI flow 0/1.18 TIMI
thresholds and glucose targets. Until such a trial is completed,
myocardial blush grade of 2 or more (88% versus 60%,
and based on the balance of current evidence,99–101 the writinggroup concluded that it was prudent to change the recommen-
Recommendation for Thrombus Aspiration During PCI
dation for the use of insulin to control blood glucose in STEMI
for STEMI
from a Class I to a Class IIa recommendation (Level of Evidence:
2009 Joint STEMI/PCI Focused Update
B) and to recommend treatment for hyperglycemia greater than
180 mg/dL while avoiding hypoglycemia.
Class IIa
7. Recommendation for Thrombus Aspiration
1. Aspiration thrombectomy is reasonable for
New recommendation
During PCI for STEMI
patients undergoing primary PCI.17,18,102(Level of Evidence: B)
December 1, 2009
Recommendations for the Use of Stents in STEMI
2009 Joint STEMI/PCI Focused Update
Class IIa
1. It is reasonable to use a DES as an alternative to a
New recommendation
BMS for primary PCI in STEMI.11,105 (Level ofEvidence: B)*
Class IIb
2007 PCI Guideline Update, Table 16
1. A DES may be considered for clinical and anatomic settings
1. A DES may be considered for clinical and anatomic
Modified recommendation (level of
in which the effectiveness/safety profile appears favorable
settings† in which the efficacy/safety profile appears
evidence changed from C to B).
but has not been fully confirmed by clinical trials. (Level of
favorable.106–109 (Level of Evidence: B)
Evidence: C)
*Consideration for the use of stents (DES or BMS) in STEMI should include the ability of the patient to comply with prolonged dual-antiplatelet therapy, the bleeding
risk in patients undergoing chronic oral anticoagulation, and the possibility that the patient may need surgery during the ensuing year.28
†For example, small vessels, long lesions, or diabetes mellitus. This recommendation applies to primary and nonprimary PCI patients with STEMI.
P⬍0.001) and 90-minute ST-segment resolution greater than
cautiously. Additionally, duration of clopidogrel therapy was
70% (64% versus 39%, P⬍0.001) occurred more frequently
longer in the DES group.
in the thrombus aspiration group. Infarct size measured by
More recently, several relatively small randomized clinical
contrast-enhanced magnetic resonance imaging in 75 patients
trials have shown an inconsistent efficacy for DES over BMS
at 3 months was significantly reduced only in the thrombus
in primary PCI. Three meta-analyses of these trials have
aspiration group.
concluded that there were no differences in death, MI, or stent
Both of these trials, as well as a meta-analysis by Bavry et
thrombosis rates, but TVR rates were decreased with
al103 and a large pooled analysis of randomized trials,104
DES.115–117 Variably included were 12 studies that differed in
support the use of aspiration thrombectomy for STEMI. In
trial design, inclusion criteria, end-point definitions, stent
developing a recommendation for the role of routine aspira-
types, duration of clopidogrel treatment, and type of
tion thrombectomy, however, it is noteworthy that TAPAS
follow-up (angiographic versus clinical). They were limited
was a study of routine thrombus aspiration versus no throm-
by sample size and duration of follow-up and by usually
bus aspiration rather than a study of routine thrombus
requiring angiographic documentation of stent thrombosis,
aspiration versus selective thrombus aspiration. It is not
which may have underestimated its true incidence.
known whether a strategy of selective thrombus aspiration in
The HORIZONS-AMI trial randomized, in a 3-to-1 ratio,
patients with a large thrombus burden might be superior to no
3006 patients to DES or BMS.9,68,105 There was no differ-
thrombus aspiration or equivalent to routine thrombus aspi-
ence in the 12-month composite safety end point of death,
ration. Clinically, it is reasonable to assume that this strategy
reinfarction, stroke, or stent thrombosis. The rates of
can be useful in STEMI patients with short ischemic times
ischemia-driven TVR and target-lesion revascularization
and large thrombus burden. It may not be helpful in STEMI
were significantly lower in the DES group (5.8% versus
patients with long ischemic times, side branches with small
8.7% and 4.5% versus 7.5%, respectively; NNT⫽33 at 1
infarct territories, or lesions with low thrombus burden.
year), as was the 13-month binary restenosis rate (10.0%versus 22.9%).
8. Recommendations for the Use of Stents
In summary, there appears to be no difference between
BMS and DES in mortality or MI rates and no difference in
stent thrombosis risk. The major advantage of DES over BMS
8.1. Stent Selection for STEMI
is a small reduction in TVR rates. Given cost considerations,
Primary PCI is generally the preferred reperfusion strategy
it could be argued that selective use of DES to prevent
for patients with STEMI.110 Compared with balloon angio-
restenosis and TVR in high-risk patients (ie, patients with
plasty, routine BMS implantation during primary PCI de-
diabetes) and in high-risk lesions (longer and smaller-
creases risk for TVR and possibly reduces MI rates but does
diameter stents) could be recommended,118 as it has been for
not reduce mortality rates.111,112
elective PCI. The greatest challenge in selecting patients for
Two-year data from the Massachusetts registry113 from
DES implantation, however, is determining in an emergency
1221 propensity score–matched pairs of DES and BMS
situation whether the patient is a candidate for prolonged
patients demonstrated a reduction in mortality and TVR rates
thienopyridine therapy. As with elective procedures, DES
with DES in primary PCI, and an analysis from the New York
should be avoided in the presence of financial barriers to
State registry114 found a reduction in mortality rates but not
continuing prolonged dual-antiplatelet therapy, social barriers
TVR rates with DES. These reports were limited to patients
that may limit patient compliance, or medical issues that
treated before 2005, so they represent the earliest experience
involve bleeding risks or the need for invasive or surgical
with DES, in which selection bias may have influenced stent
procedures in the following year that would interrupt anti-
choice and off-label use may have been pursued more
platelet therapy.
Kushner et al
2009 Focused Updates: STEMI and PCI Guidelines
Recommendation for Angiography in Patients With Chronic Kidney Disease
2004/2005/2007 Recommendation: 2007 PCIGuidelines Update, Table 9
2009 PCI Focused Update Recommendation
2. In chronic kidney disease patients undergoing
1. In patients with chronic kidney disease undergoing angiography
Modified recommendation
angiography, isosmolar contrast agents are
who are not undergoing chronic dialysis, either an isosmolar
(changed text).
indicated and are preferred. (Level of Evidence: A)
contrast medium19,119 (Level of Evidence: A) or alow-molecular-weight contrast medium other than ioxaglate oriohexol is indicated.19 (Level of Evidence: B)
PCI Focused Update Section
the only ionic LOCM (RR 0.58, CI 0.37 to 0.92, P⫽0.02124),and with iohexol, a nonionic LOCM (RR 0.19 to 0.38,
9. Recommendation for Angiography in Patients
P⬍0.01124,125), but no difference was noted in comparisons of
With Chronic Kidney Disease
iodixanol with iopamidol, iopromide, or ioversal,124 and a
single trial favored iomeprol.123 A pooled comparison of
9.1. Angiography in Patients With Chronic
iodixanol with all nonionic LOCM other than iohexol indi-
cated equivalent safety (RR 0.97; CI 0.72 to 1.32,
Patients with chronic kidney disease (CKD) with or without
P⫽0.86125). Results were consistent regardless of ancillary
diabetes who undergo angiography are at high risk for a
preventive therapies (hydration, acetylcysteine), route of
contrast-induced nephropathy (CIN). At issue is the selection
administration (intravenous or intra-arterial), age, sex, dose,
of a contrast agent to minimize this risk. The 2007 UA/
or preexisting CKD or diabetes. Of further interest, findings
NSTEMI guideline recommended that in patients with
were similar in the 8 studies (n⫽1793 patients) performed in
chronic kidney disease undergoing angiography, "isosmolar
the setting of coronary angiography.124
contrast agents are indicated and are preferred (Level of
These more recent observations indicate that the CIN risk
Evidence: A)" (p e112).97 In patients with CKD or CKD and
of contrast media cannot be attributed to osmolarity alone, but
diabetes mellitus who are undergoing angiography, isosmolar
that ionicity and other and unknown characteristics of spe-
contrast material was shown to lessen the rise in creatinine.
cific agents may play a role. Thus, the updated evidence base
This was based on evidence up to mid-2007 that suggested
suggests that the recommended choices of contrast media
that isosmolar agents also reduced the risk of CIN in both a
during coronary angiography be expanded to either isosmolar
moderate-sized randomized clinical trial (RECOVER [Renal
media or LOCM other than ioxaglate or iohexol.
Toxicity Evaluation and Comparison Between Visipaque(Iodixanol) and Hexabrix (Ioxaglate) in Patients With Renal
10. Recommendations for Use of Fractional
Insufficiency Undergoing Coronary Angiography]) that com-
Flow Reserve
pared iodixanol with ioxaglate119 and a meta-analysis of 16
smaller, earlier clinical trials.120
10.1. Fractional Flow Reserve
However, in mid-2007, a major US randomized trial of
Coronary angiography is often performed in clinical situa-
contrast agents in patients with CAD and an estimated
tions in which preprocedural functional testing has not been
glomerular filtration rate of 20 to 59 mL/min who were
obtained. Additionally, in the setting of multivessel disease,
undergoing angiography, the CARE study, was published.
the need to treat individual stenosis is often difficult to
CARE compared the low-osmolar agent iopamidol and the
determine. Although revascularization of ischemia-producing
isosmolar agent iodixanol and found no difference in the
lesions improves patient outcomes, the clinical benefits of
primary end point (serum creatinine increase of 0.5 mg/dL or
revascularization of stenotic but non–ischemia-producing le-
higher over baseline) between iopamidol (4.4%) and iodixa-
sions are less clear. Intraprocedural assessment of the func-
nol (6.7%, P⫽0.39).19
tional significance of individual stenosis may help define the
Since then, several larger randomized trials have been
optimal revascularization strategy.
published that reported no difference in CIN when iodixanol
The objective of the FAME trial20 was to compare clinical
was compared with various other low-osmolar contrast media
outcomes after PCI on the basis of conventional angiographic
(LOCM).19,121–123 These and other randomized trials compar-
determination of lesion severity versus fractional flow reserve
ing isosmolar iodixanol with LOCM have been summarized
(FFR) combined with angiography in patients with multivessel
in 2 mutually supportive and complementary meta-analyses
disease. This prospective, randomized, multicenter trial included
involving 16 trials in 2763 patients124 and 25 trials in 3260
1005 patients selected from 1905 screened patients at 20 medical
patients,125 respectively. When more recent trials were com-
centers who were randomized to either angiography-guided or
bined with the older studies, trends in CIN favoring iodixanol
FFR-guided (for lesions with FFR less than or equal to 0.80)
were no longer significant (summary RR 0.79; 95% CI 0.56
PCI. Before randomization, lesions that required PCI were
to 1.12; P⫽0.29; summary RR 0.80; CI 0.61 to 1.04; P⫽0.10,
prespecified on the basis of the angiographic appearance. Pa-
respectively).124,125 However, subanalyses showed variations
tients assigned to angiography-guided PCI had all identified
in relative renal safety by specific LOCM: A reduction in CIN
lesions treated with DES, whereas those assigned to FFR-guided
was observed when iodixanol was compared with ioxaglate,
PCI had only identified lesions with an FFR of 0.80 or less
December 1, 2009
Table 10.
Recommendations for Use of Fractional Flow Reserve
2004/2005/2007 Recommendation: 2005 PCIGuideline, Section 5.6.2.
2009 PCI Focused Update Recommendations
Class IIa
1. It is reasonable to use intracoronary physiologic
1. Coronary pressure (fractional flow reserve 关FFR兴) or Doppler
Modified recommendation (level of
measurements (Doppler ultrasound, fractional
velocimetry can be useful to determine whether PCI of a
evidence changed from B to A
flow reserve) in the assessment of the effects of
specific coronary lesion is warranted. FFR or Doppler
for FFR; C for Doppler).
intermediate coronary stenoses (30% to 70%
velocimetry can also be useful as an alternative to
luminal narrowing) in patients with anginal
performing noninvasive functional testing (eg, when the
symptoms. Coronary pressure or Doppler
functional study is absent or ambiguous) to determine
velocimetry may also be useful as an alternative
whether an intervention is warranted. It is reasonable to
to performing noninvasive functional testing (eg,
use intracoronary physiological measurements (coronary
when the functional study is absent or
pressure 关FFR兴20,126–137 关Level of Evidence: A兴 or Doppler
ambiguous) to determine whether an
velocimetry 关Level of Evidence: C兴) in the assessment of
intervention is warranted. (Level of Evidence: B)
the effects of intermediate coronary stenoses (30% to 70%luminal narrowing) in patients with anginal symptoms.
Class III
1. Routine assessment with intracoronary
1. Routine assessment with intracoronary physiological
Modified recommendation
physiologic measurements such as Doppler
measurements such as coronary pressure (FFR) or Doppler
ultrasound or fractional flow reserve to assess
ultrasound to assess the severity of angiographic disease in
the severity of angiographic disease in patients
concordant vascular distribution in patients with angina and
with a positive, unequivocal noninvasive
a positive, unequivocal noninvasive functional study is not
functional study is not recommended. (Level of
recommended. (Level of Evidence: C)
Evidence: C)
treated with DES. The primary end point of the trial was the rate
Evidence B recommendation for patients who are not eligible
of death, nonfatal MI, and repeat revascularization at 1 year.
for CABG. Thus, it has been recommended that CABG still
No difference was evident in the number of intended
be considered the standard of care for left main CAD.147–149
lesions to be treated per patient (2.7⫾0.9 versus 2.8⫾1.0,
Several studies comparing CABG to PCI, however, indi-
P⫽0.34) in the angiography- and FFR-guided groups, respec-
cated that the advantage of CABG consists primarily of fewer
tively. In the FFR group, 37% of lesions had an FFR greater
repeat revascularizations.139,149–155 The study by Brener et
than 0.80. Evaluation of ischemia, as defined by an FFR less
al156 indicates no significant mortality difference between
than 0.80, resulted in fewer lesions receiving stents (2.7⫾1.2
PCI and CABG after 3 years of follow-up. Longer-term
versus 1.9⫾1.3, P⬍0.001). At 1 year, the composite event
follow-up is needed.
rate was 18.3% in the angiography-guided group compared
The present focused update specifically addresses the
with 13.2% in the FFR-guided group (P⫽0.02).
findings of SYNTAX, an unblinded, randomized clinical trial
The results of the FAME trial suggest that identification of
that assigned patients with 3-vessel and/or left main CAD to
ischemia-producing lesions by use of systematic assessment
an initial treatment strategy of CABG or PCI.21 The primary
of FFR in patients undergoing multivessel PCI is associated
prespecified end point for the 1800 enrolled patients was the
with improved clinical outcomes compared with angio-
composite of death, stroke, and myocardial revascularization
graphic assessment alone. Further evidence is needed regard-
determined at 12 months. Prespecified stratification occurred
ing the added value of assessing FFR in lesions with greater
for diabetes mellitus and left main CAD. Ninety-seven
than 90% stenosis.
percent of CABG patients received at least 1 arterial graft.
In SYNTAX, for the subgroup with left main CAD, there
11. Recommendations for PCI for Unprotected
were no significant differences in the incidence of the
Left Main Coronary Artery Disease
composite end point (death, MI, stroke, or repeat revascular-
ization) between the 2 groups (PCI 15.8% versus CABG13.7%, P⫽0.44), although rates of repeat revascularization
11.1. Unprotected Left Main Coronary Artery Disease
were higher (11.8% versus 6.5%, P⫽0.02) and rates of stroke
Although listed as a Class III indication in the 2003 guideline
were lower (0.3% versus 2.7%, P⫽0.01) in the PCI group.21
on the management of chronic stable angina,145 PCI of an
Left main stented patients with limited CAD (lower SYNTAX
unprotected left main coronary artery has increased in fre-
score) displayed a trend toward fewer adverse events at 12
quency.146 Early studies (listed in Appendix 6) involved short
months than did similar patients assigned to CABG. Specifi-
follow-up periods, which gave CABG a disadvantage, be-
cally, MACE in patients with isolated left main CAD oc-
cause the apparent benefits of surgery over PCI in other
curred in 8.5% with CABG versus 7.1% with PCI, and in
settings have not typically been fully evident until 1 to 5 years
13.2% with CABG versus 7.5% with PCI in patients with left
after the procedure. In the ACC/AHA/SCAI 2005 guideline
main CAD and disease of 1 other vessel. In contrast, MACE
update for PCI, the performance of PCI for left main CAD is
with CABG versus PCI were numerically less frequent in
given a Class III, Level of Evidence C recommendation if the
patients with disease of the left main coronary artery and
patient is eligible for CABG and a Class IIa, Level of
disease of 2 other vessels (14.4% versus 19.8%) and in
Kushner et al
2009 Focused Updates: STEMI and PCI Guidelines
Table 11.
Recommendations for PCI for Unprotected Left Main Coronary Artery Disease
2009 PCI Focused Update Recommendations
Class IIa
2005 PCI Guideline, Section 6.3.4.
1. It is reasonable that patients undergoing PCI to
Deleted recommendation (no longer
unprotected left main coronary obstructions be
followed up with coronary angiographybetween 2 and 6 months after PCI. (Level ofEvidence: C)
Class IIb
1. PCI of the left main coronary artery with stents as an
New recommendation
alternative to CABG may be considered in patientswith anatomic conditions that are associated with alow risk of PCI procedural complications and clinicalconditions that predict an increased risk of adversesurgical outcomes.*21,138,139 (Level of Evidence: B)
Class III
2005 PCI Guideline, Section 5.1
PCI is not recommended in patients with 关. . 兴
Modified recommendation (bullet "f" from
f. Left main disease and eligibility for CABG.
Section 5.1 and bullet "e" from
(Level of Evidence: C)
Sections 5.2. and 5.3. are no longer
2005 PCI Guideline, Sections 5.2, 5.3
current; see 2009 Class IIb
PCI is not recommended in patients with 关. . 兴
recommendation #1).
e. Left main disease and eligibility for CABG.
(Level of Evidence: C)
*Stenting for unprotected left main CAD is relatively more favorable for patients with isolated left main coronary artery lesions or left main coronary artery plus
single-vessel disease,21 for patients with ostial or mid left main coronary artery lesions,138,140–144 and for patients with factors (such as severe lung disease, priorthoracic surgery, or poor bypass graft targets) that would make CABG a high-risk procedure or unlikely to be successful. Conversely, CABG surgery for unprotectedleft main CAD may be relatively more favorable for patients with left main CAD plus multivessel disease,21 distal/bifurcation left main coronary artery lesions,138,140–144or low surgical risk with a good chance of technical success.
patients with both left main CAD and 3 other vessels
with left main and 2- or 3-vessel disease compared with
involved (15.4% versus 19.3%).21
patients with left main and no other vessel or 1-vessel disease
These data from a post hoc subgroup analysis in SYNTAX
had higher rates of MACE, it is recommended that PCI to left
must be interpreted with caution for several reasons. The number
main lesions be limited to patients without significant mul-
of patients with isolated left main (or left main plus single
tivessel disease. Second, because of the narrow margin for
vessel) CAD was relatively small, and the differences in out-
error, operators undertaking PCI of left main coronary lesions
comes were not statistically significant. Furthermore, SYNTAX
should be experienced and backed by highly competent
reported outcomes at 1 year, and longer follow-up is needed
support staff and surgeons.157 Although routine use of intra-
before left main PCI (in patients who are otherwise surgical
vascular ultrasound has been advocated by some authors for
candidates) should become standard clinical practice. Moreover,
the evaluation of left main lesions, there is no definitive
because the overall study did not reach its primary end point,
evidence at present that this technique improves out-comes.138,157 Finally, not all left main lesions respond equally
subset analyses are less robust; because noninferiority was not
well to PCI. Bifurcation lesions are technically more chal-
proven in this cohort, specific information for each subgroup is
lenging138 and have higher rates of restenosis.140,141,143,144 In
of an observational nature and is hypothesis-generating.
contrast, results of PCI of ostial or mid-body left main
On the basis of the evidence in aggregate, prior to and
coronary lesions more closely approximate the results of
within the present focused update, the writing group has
CABG, even with respect to the need for subsequent proce-
modified the class of recommendation for PCI to unprotected
dures.142 The best case for PCI as an alternative to CABG for
left main coronary from Class III to Class IIb, now citing the
left main CAD is in ostial and mid-body lesions without
Level of Evidence as B. The writing group noted 3 important
additional multivessel disease.
caveats in classifying unprotected left main CAD as a Class
The writing group discussed the previous Class IIa recom-
IIb indication. First, patients undergoing PCI in cohort or
mendation for follow-up between 2 and 6 months with
randomized studies represent merely a subset of all patients
coronary angiography. They focused on the inability of
with left main CAD. Because only certain left main coronary
angiography to predict a situation that might be prone to
lesions are amenable to PCI, the Class IIb indication is
acute, sudden stent thrombosis, as well as the risk associated
intended to apply only to those left main lesions that are
with angiography in a patient who has undergone placement
suitable for PCI. The primary conclusion of SYNTAX is that
of a left main stent. In view of these factors, the writing group
PCI failed to be shown to be noninferior to CABG in left
decided that the Class IIa recommendation for angiographic
main and triple-vessel disease. Because patients in SYNTAX
follow-up should be omitted from the guidelines.
December 1, 2009
Table 12.
Recommendations for the Timing of Angiography and Antiplatelet Therapy in UA/NSTEMI
2009 PCI Focused Update Recommendations
1. Patients with definite or likely UA/NSTEMI selected for an invasive approach should receive
New recommendation
dual-antiplatelet therapy.158,159 (Level of Evidence: A) Aspirin should be initiated on presentation.158,159(Level of Evidence: A) Clopidogrel (before or at the time of PCI)158,159 (Level of Evidence: A) orprasugrel (at the time of PCI)27 (Level of Evidence: B) is recommended as a second antiplatelet agent.
Class IIa
1. It is reasonable for initially stabilized high-risk patients with UA/NSTEMI* (GRACE 关Global Registry of
New recommendation
Acute Coronary Events兴 risk score greater than 140) to undergo an early invasive strategy within 12to 24 hours of admission. For patients not at high risk, an early invasive approach is alsoreasonable.22,23 (Level of Evidence: B)
*Immediate catheterization/angiography is recommended for unstable patients.
12. Recommendations for the Timing
to early intervention; major bleeding occurred in 3.1% of
of Angiography and Antiplatelet Therapy
patients in the early invasive group and 3.5% in the delayed
in UA/NSTEMI
invasive group.
Overall in TIMACS, early intervention trended to be
superior to delayed intervention in preventing the composite
12.1. Timing of Angiography
of death, MI, or stroke (primary end point), but the difference
A routine invasive strategy in UA/NSTEMI patients with
was not statistically significant.23 However, early intervention
high-risk features has been associated with improved out-
reduced the composite of death, MI, or refractory ischemia
comes, but the optimal timing of intervention has not been
(the secondary end point) and, in high-risk patients, was
well established. Early intervention might prevent ischemic
superior to a delayed invasive strategy. The trial was under-
events that could occur while the patient awaits a delayed
powered to discern a clinically meaningful 15% advantage to
procedure. Alternatively, with intensive antithrombotic ther-
early invasive therapy for the primary end point, with
apy with a delay for up to a few days, procedure-related
recruitment stopped at 3000 because of recruitment and
complications might be avoided by intervening on a more
funding challenges. This provided a power of 80% to detect
stable, "passivated" plaque. Although one study has sug-
a risk reduction of 28% in the primary end point. Subgroup
gested greater benefit with relatively early intervention,106 the
analysis (high-risk subset) of this overall negative trial was
evidence base for a definitive recommendation on timing isweak. Thus, the question of when to intervene in UA/
not robust and must be viewed cautiously.
NSTEMI has not been answered conclusively. Given this
Taken together with the earlier ISAR-COOL (Intracoro-
uncertainty, the TIMACS investigators23 undertook a large,
nary Stenting With Antithrombotic Regimen Cooling Off)
multicenter randomized trial to determine whether a strategy
study,106 the favorable secondary end-point results, the sub-
of early coronary angiography and intervention was superior
group analysis in patients at higher risk, and the lack of a
to a delayed strategy in patients with UA/NSTEMI assigned
safety issue with early therapy, TIMACS suggests the fol-
to an invasive approach.
lowing conclusions: an early invasive strategy within 12 to 24
TIMACS randomly assigned 3031 non–ST-elevation ACS
hours (median 14 hours) is preferred in high-risk patients and
patients to routine early intervention (coronary angiography
may be chosen in patients at low to intermediate risk at the
within 24 hours) or to delayed intervention (coronary angiogra-
physician's or institution's preference (eg, efficiency and cost
phy at 36 hours or more). The primary outcome was the
savings), whereas a more delayed approach may be beneficial
composite of death, MI, or stroke at 6 months, and a prespecified
in low- to intermediate-risk patients.23 In contrast, results
secondary outcome was death, MI, or refractory ischemia.23
from the recent ABOARD (Angioplasty to Blunt the rise Of
Coronary angiography was performed at a median of 14 hours
troponin in Acute coronary syndromes Randomized for an
in the early-intervention group and 50 hours in the delayed-
immediate or Delayed intervention) trial160 indicate that an
intervention group. At 6 months, 9.7% of patients in the
immediate invasive strategy (median time 1.1 hour) in UA/
early-intervention group experienced a primary outcome versus
NSTEMI is not associated with further incremental benefit.
11.4% in the delayed-intervention group (HR 0.85; 95% CI 0.68
Typically, early versus delayed angiography is defined
to 1.06; P⫽0.15). Death, MI, or refractory ischemia was reduced
with reference to a 12- to 48-hour time window. The
by 28% in favor of early intervention (9.6% versus 13.1%; HR
ISAR-COOL study106 supports an earlier compared with a
0.72; 95% CI 0.58 to 0.89; P⫽0.002). Prespecified analyses
more delayed time to angiography, but the data supporting
showed that early intervention improved the primary outcome in
this general timing suggestion are limited.
the one third of patients at highest risk (HR 0.65; 95% CI 0.48to 0.88), as determined by a GRACE (Global Registry of Acute
12.2. Timing of GP IIb/IIIa Receptor Antagonist Therapy
Coronary Events) risk score greater than 140, but not in the two
in UA/NSTEMI Patients Undergoing Angiography
thirds at low to intermediate risk (HR 1.14; 95% CI 0.82 to 1.58;
The optimal timing of initiation of GP IIb/IIIa receptor
P for heterogeneity⫽0.01). There were no safety issues related
antagonist therapy in patients with UA/NSTEMI (ie, whether
Kushner et al
2009 Focused Updates: STEMI and PCI Guidelines
to administer therapy upstream on presentation or later at the
the use of eptifibatide at PCI (39% of patients in the delayed,
time of angiography/PCI) and the optimal application of this
provisional group), EARLY ACS does not contradict the benefit
therapy (ie, whether routine, selective, or provisional) have
of GP IIb/IIIa therapy over placebo in UA/NSTEMI in previous
not been resolved. The 2007 ACC/AHA Guidelines for the
studies. Rather, its findings relate specifically to the timing of
Management of Patients With UA/NSTEMI recommend that
such therapy and selective versus routine use.
patients with definite or likely UA/NSTEMI selected for an
In another similar study, ACUITY (Acute Catheterization
invasive approach should receive ASA and either clopidogrel
and Urgent Intervention Triage strategY), superiority of early
or a GP IIb/IIIa receptor antagonist before angiography
GP IIb/IIIa therapy also was not found, but investigators
(Class I, Level of Evidence: A).97 They further state that it is
could not exclude as much as a 29% benefit with GP IIb/IIIa
reasonable to initiate both clopidogrel and a GP IIb/IIIa
therapy nor show noninferiority of delayed administration. In
receptor antagonist, especially in the setting of delays to
addition, drug exposure before angiography was much shorter
angiography, high-risk features, or recurrent ischemic discom-
(4 hours), which might substantially diminish the opportunity
fort (Class IIa, Level of Evidence: B). The 2007 European
for differential efficacy.161
Society of Cardiology guidelines recommend early dual-
The results of the EARLY ACS study are similar to a
antiplatelet therapy with ASA and clopidogrel (Class I), with the
meta-analysis of 6 prior large, randomized trials of GP IIb/IIIa
addition of a GP IIb/IIIa receptor antagonist for those patients
therapy versus placebo in non–ST-elevation ACS in which an
with the specific high-risk features of an elevated troponin level,
invasive strategy was not mandated, which showed a relative
ST-segment depression, or diabetes (Class IIa).163
reduction in death/MI of 9% (CI 2% to 16%).162 In those patients
The EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in
who underwent PCI, the RR reduction was a more robust 23%
Patients With Non–ST-Segment Elevation Acute Coronary Syn-
(CI 8% to 36%). This finding also was consistent with EARLY
drome) trial22 tested the hypothesis that a strategy of early,
ACS. Both studies found no benefit in troponin-negative pa-
routine administration of the GP IIb/IIIa receptor antagonist
tients. The investigators ascribed the less than expected benefit
eptifibatide would be superior to delayed, provisional adminis-
of early GP IIb/IIIa therapy in EARLY ACS to convergence of
tration in reducing ischemic complications among high-risk
eptifibatide use in the 2 arms at the time of PCI and more
patients. EARLY ACS enrolled 9492 non–ST-segment eleva-
aggressive contemporary cotherapies compared with earlier
tion ACS (UA/NSTEMI) patients who presented within 24
studies, including frequent use of clopidogrel, low-molecular-
hours of an episode of ischemic rest discomfort and who were
weight heparin, and statins. A further caution is the lack of
assigned to an invasive treatment strategy no sooner than the
follow-up for several years.
next calendar day (amended later to at least 12 hours but less
Despite a lack of clarity from the overall and subgroup
than 96 hours after randomization). Eligibility required at least 2 of
results, an argument can be made against the routine upstreamuse of GP IIb/IIIa therapy in all non–ST-elevation ACS
the following features: ST-segment depression or transient ST-
patients intended for an invasive strategy. In particular, those
segment elevation, an elevated biomarker (creatine kinase-MB or
with a normal baseline troponin level and those over the age
troponin), and age of 60 years or older (amended to include patients
of 75 years, in whom there was no evidence for benefit but
50 to 59 years with known vascular disease). The key primary end
who showed an increased risk of bleeding, might be ex-
point was all-cause death, MI, recurrent ischemia that required
cluded. On the other hand, findings in those with a positive
urgent revascularization, or thrombotic bailout at 96 hours. The key
troponin at baseline and those with diabetes, although not
secondary efficacy end point was all-cause death or MI within 30
definitive in EARLY ACS alone, trend positively and are in
days. Safety end points included major hemorrhage and transfu-
line with previous results. The EARLY ACS trial showed no
sions through 120 hours after randomization. The study was
significant benefit in the composite outcome comparing early
powered to detect 22.5% and 15% relative reductions in the primary
versus delayed eptifibatide as defined by the study. Thus, at
and key secondary end points, respectively.
this time, a high-risk group that would clearly benefit from
The primary end point occurred in 9.3% of patients in the
the early administration of eptifibatide upstream before car-
early therapy arm versus 10.0% of patients in the provisional
diac catheterization has not been identified. Early GP IIb/IIIa
GP IIb/IIIa therapy arm (odds ratio 0.92; 95% CI 0.80 to 1.06;
therapy in patient groups continues to appear reasonable if
P⫽0.23). Secondary end-point event rates were 11.2% versus
they are judged clinically to be at high risk of thrombotic
12.3% (odds ratio 0.89; CI 0.79 to 1.01; P⫽0.08). Early,
events relative to bleeding risk.
routine eptifibatide administration occurred at the cost of agreater risk of TIMI major hemorrhage (2.6% versus 1.8%,
P⫽0.02). Moderate and less severe bleeding also occurredmore commonly. Rates of red cell transfusion were 8.6% and
American College of Cardiology Foundation
6.7%, respectively (P⫽0.001).
John C. Lewin, MD, Chief Executive OfficerCharlene May, Senior Director, Science and Clinical Policy
EARLY ACS represents a large, carefully executed trial with
Lisa Bradfield, CAE, Associate Director, Science and Clinical Policy
potentially important implications; however, these results are
Leigh Maltese, Specialist, Science and Clinical Policy
best taken in the context of previous major trials. As a single
Debjani Mukherjee, MPH, Associate Director, Evidence-Based Medicine
trial, EARLY ACS does not establish the superiority of early
Erin A. Barrett, Senior Specialist, Science and Clinical Policy
versus delayed, provisional eptifibatide in non–ST-elevation
American Heart Association
ACS. A trend toward fewer recurrent ischemic complications
Nancy Brown, Chief Executive Officer
was noted at 30 days, but this was counterbalanced by more
Rose Marie Robertson, MD, FACC, FAHA, Chief Science Officer
frequent episodes of bleeding and need for transfusions. Given
Judy Bezanson, DSN, CNS, RN, Senior Science and Medicine Advisor
December 1, 2009
Appendix 1.
Author Relationships With Industry and Other Entities—ST-Elevation Myocardial Infarction
or Other Financial
Frederick G.
Tulane University School of
Abbott; Bristol-Myers Squibb
Professor of Medicine;
Agency for Healthcare
Quality—Health Science
Brigham and Women's
Sanofi-aventis; Eli Lilly
Accumetrics; Amgen, Inc; AstraZeneca
Pharmaceuticals; Bayer Healthcare; Beckman
Coulter; Biosite; Bristol-Myers Squibb
Pharmaceutical Research Institute; CV
Therapeutics; Daiichi-Sankyo*; Eli Lilly*;
GlaxoSmithKline; Inotek Pharmaceuticals Corp;
Integrated Therapeutics Corp; Merck;
Millennium Pharmaceuticals; National
Institutes of Health; Novartis Pharmaceuticals;
Nuvelo; Ortho Clinical Diagnostics; Pfizer;
Roche Diagnostics Corp; Roche Diagnostics
GmbH; Sanofi-aventis*; Sanofi-Synthelabo
Recherche; Schering-Plough Research Institute
Boehringer Ingelheim;
Michigan—Professor of
Daiichi-Sankyo; Eli Lilly;
Eli Lilly; Novartis;
Atlantic Health—Chief
Medical Officer and Vice
President of Quality
University of Michigan
—Associate Professor,
Dept. of Family Medicine
New York University School
Bayer HealthCare AG; Eli Lilly; Johnson &
of Medicine—Clinical Chief
Johnson Pharmaceutical Research &
Development; Millennium Pharmaceuticals;
Schering-Plough Research Institute
Yale University School of
Centers for Medicare and Medicaid Services*
Hines, Jr. Professor of
Medicine and Epidemiology
and Public Health
Virginia Commonwealth
University Health
System—Professor and
Chair, Dept. of Emergency
Georgetown University
Hospital—Professor of
University of South
Boehringer Ingelheim;
Anoxic Encephalopathy,
Florida—Professor and
Genentech; National
2006; Acute Stroke
Director, USF Stroke
Association for Continuing
2006–2007; Carotid
Endarterectomy, 2006
Center for Cardiovascular
Medicine—Professor of
Medicine; Director
This table represents the relationships of committee members with industry that were reported at the Task Force on Practice Guidelines meeting and updated in conjunction with all meetings. A person is deemed
to have a significant interest in a business if the interest represents ownership of 5% or more of the voting stock or share of the business entity or ownership of $10 000 or more of the fair market value of the business
entity, or if funds received by the person from the business entity exceed 5% of the person's gross income for the previous year. A relationship is considered to be modest if it is less than significant under the preceding
definition. Relationships noted in this table are modest unless otherwise noted.
*Significant (greater than $10 000) relationship.
Kushner et al
2009 Focused Updates: STEMI and PCI Guidelines
Appendix 2.
Author Relationships With Industry and Other Entities—Percutaneous Coronary Intervention
or Other Financial
Center for Cardiovascular Science
Smith, Jr, Chair
and Medicine—Professor of
Medicine; Director
Saint Joseph's Heart and Vascular
Abbott; AngelMed; BG
III, Co-Chair
Intermountain Medical
Center—Associate Chief of
Daiichi-Sankyo; Eli
University of Texas Medical
Abbott; BSCI; Cordis;
Center—Professor of Medicine
Volcano Therapeutics
Geisinger Medical
Director, Cardiac Cath Lab
Boston University School of
Medicine—Professor of Medicine;
Accumetrics; Cordis;
Boston University Medical
Research Institute
Catheterization Laboratories and
Duke Clinical Research Institute,
Duke University Medical
Center—Professor of Medicine;
aventis*; Merck*;
Director, Cardiovascular Research
Cleveland Clinic Foundation, Dept.
ICON Plc; Medlogics;
of Cardiovascular
Brigham and Women's Hospital
Boston Biomedical
Volcano Therapeutics
DSMB indicates data and safety monitoring board; SCAI, Society for Cardiovascular Angiography and Interventions.
This table represents the relationships of committee members with industry that were reported at the Task Force on Practice Guidelines meeting and updated in
conjunction with all meetings. A person is deemed to have a significant interest in a business if the interest represents ownership of 5% or more of the voting stockor share of the business entity or ownership of $10 000 or more of the fair market value of the business entity, or if funds received by the person from the businessentity exceed 5% of the person's gross income for the previous year. A relationship is considered to be modest if it is less than significant under the precedingdefinition. Relationships noted in this table are modest unless otherwise noted.
*Significant (greater than $10 000) relationship.
December 1, 2009
Appendix 3.
Reviewer Relationships With Industry and Other Entities—2009 STEMI and PCI Focused Updates
or Other Financial
Eli Lilly*; Ischemix LLC
Boehringer Ingelheim (Canada)
Ltd*; Eli Lilly*; Portola
Pharmaceuticals Inc*;
Sanofi-aventis Canada Inc*;
Schering-Plough Research
Institute*; Uppsala Clinical
Research Center and
Christopher E.
Practice Guidelines
Board of Governors
United Health Care
Biophysical*; Paragon
antithrombotic therapy
Board of Trustees
for an individual with
Boston Scientific*; Medtronic*;
The Medicines Co*
Bayer; Boehringer
Ingelheim; Exeter CME;
Johnson & Johnson; King
Roche; Sanofi-aventis
Boston Scientific;
Interventional Council
Interventional Council
Bristol-Myers Squibb;
Cogentus; Eisai*; Eli
Squibb; Daiichi-Sankyo; Eli
Lilly; Johnson & Johnson;
Heartscape*; Johnson &
Medtronic; Novartis;
Johnson; The Medicines Co;
Momenta; Portola;
Board of Governors
Interventional Council
Board of Governors
Practice Guidelines
Kushner et al
2009 Focused Updates: STEMI and PCI Guidelines
Appendix 3.
or Other Financial
Abbott Vascular; Boston
Boston Scientific
Boston Scientific
Practice Guidelines
AstraZeneca; Baxter;
AstraZeneca; Baxter;
Bayer; Bristol-Myers
Bristol-Myers Squibb*;
Research Institute
Squibb; Daiichi-Sankyo; Eli
GlaxoSmithKline*; The
Lilly; Johnson & Johnson;
Medicines Co; Merck*;
Medtronic; Ostuka
Maryland Research
Institute; Pfizer;
Schering-Plough*; WebMD*
Bayer Healthcare AG; Eli Lilly;
GlaxoSmithKline; Johnson &
Johnson Pharmaceutical
Practice Guidelines
Research & Development;
Schering-Plough Research
Board of Governors
Bristol-Myers Squibb Canada*;
Eli Lilly Canada; Medtronic
Canada*; Pfizer Canada*;
Sanofi-aventis Canada*;
Schering-Plough Canada*;
Sepracor Pharmaceuticals, Inc
Board of Governors
Board of Governors
2009, deposition for
plaintiff: air embolism
Board of Governors
Interventional Council
Sharon-Lise T.
December 1, 2009
Appendix 3.
or Other Financial
Abbott Vascular; Baxter
Abbott Vascular; AstraZeneca;
Healthcare; Boehringer
Baxter Healthcare; Berlex
Labs/Bayer HealthCare;
Therapeutics; NicOx; Pfizer;
Boehringer Ingelheim; Cardium
Therapeutics; CV Therapeutics;
Labs; GlaxoSmithKline; Merck;
Novartis; Pfizer; Reliant
Schering-Plough; The
Medicines Co; Viron
Charanjit S.
Interventional Council
Interventional Council
Boston Biomedical
Abbott Vascular; Boston
Associates*; CR Bard*;
Scientific; Medtronic
Davol*; Lab Coat*; TherOx*
Abbott Vascular*; Eli Lilly*;
AstraZeneca; Boston
Gilead Sciences*; Merck*;
Scientific; Genzyme; Gilead
Sciences; Medtronic;
Eli Lilly*; GlaxoSmithKline*;
Johnson & Johnson*; Merck
Sharpe & Dohme*; The
Medicines Co*; NIH*; Pfizer*;
Roche*; Sanofi-aventis*;
Astellas Healthcare*; GE
GE Healthcare*; Molecular
Molecular Insight
Healthcare*; King
Insight Pharmaceuticals*
ACCF indicates American College of Cardiology Foundation; AHA, American Heart Association; NHLBI, National Heart, Lung, and Blood Institute; NIH, National
Institutes of Health; and SCAI, Society for Cardiovascular Angiography and Interventions.
This table represents the relationships of peer reviewers with industry and other entities that were reported by authors to be relevant to this document. These
relationships were reviewed and updated in conjunction with all meetings and/or conference calls of the writing committee during the document development process.
The table does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a business if the interestrepresents ownership of 5% or more of the voting stock or share of the business entity or ownership of $10 000 or more of the fair market value of the businessentity, or if funds received by the person from the business entity exceed 5% of the person's gross income for the previous year. A relationship is considered to bemodest if it is less than significant under the preceding definition. Relationships in this table are modest unless otherwise noted.
*Significant (greater than $10 000) relationship.
Kushner et al
2009 Focused Updates: STEMI and PCI Guidelines
Appendix 4.
Dosing Table for Antiplatelet and Anticoagulant Therapy Discussed in This Focused Update to Support PCI in STEMI
Patient Received Initial Medical
Treatment (With an
Patient Did Not Receive Initial Medical
Anticoagulant and/or
Treatment (With an Anticoagulant
Comments: All Patients to Receive
Fibrinolytic Therapy)
and/or Fibrinolytic Therapy)
ASA (162–325 mg)
Glycoprotein IIb/IIIa ReceptorAntagonists (Section 2)
Of uncertain benefit
LD of 0.25 mg/kg IV bolus
Continue for up to 12 hours at the
MD of 0.125 mcg/kg per minute
discretion of the physician.9,11
(maximum 10 mcg/min) (Class IIa,LOE: A)
Of uncertain benefit
LD of 180 mcg/kg IV bolus followed 10
Double bolus recommended to support
minutes later by second IV bolus of
PCI in STEMI as the recommended
adult dosage of eptifibatide in
MD of 2.0 mcg/kg per minute, started
patients with normal renal
after first bolus; reduce infusion by
50% in patients with estimated
Infusion should be continued for 12 to
creatinine clearance ⬍50 mL/min
18 hours at the discretion of the
(Class IIa, LOE: B)
Of uncertain benefit
LD of 25 mcg/kg IV bolus
Increased dosing over previous
MD of IV infusion of 0.1 mcg/kg per
min; reduce rate of infusion by 50%
Continue for up to 18 hours at the
in patients with estimated creatinine
discretion of the physician.12
clearance ⬍30 mL/min (Class IIa,LOE: B)
Thienopyridines (Section 3)
If 600 mg given orally, then no
LD 300–600 mg orally
Optimum LD has not been established.
additional treatment
MD of 75 mg orally per day (Class I,
Dose for patients ⬎75 years of age
A second LD of 300 mg may
has not been established.
be given orally to
There is a recommended duration of
supplement a prior LD of
therapy for all post-PCI patients
300 mg (Class I, LOE: C)
receiving a BMS or DES.
Period of withdrawal before surgery
should be at least 5 days.
(For full explanations, see footnote.)
No data are available to guide
LD of 60 mg orally
There is no clear need for treatment
MD of 10 mg orally per day (Class I,
with prasugrel before PCI.
MD of 5 mg orally per day in special
Special dosing for patients ⬍60 kg or
⬎75 years of age.
There is a recommended duration of
therapy for all post-PCI patientsreceiving a DES.
Contraindicated for use in patients
with prior history of TIA or stroke.
(For full explanations, see footnote.)
Parenteral Anticoagulants(Section 4)
For patients who have received
0.75 mg/kg bolus, 1.75 mg/kg per hour
Bivalirudin may be used to support PCI
UFH, wait 30 minutes, then
and STEMI with or without
give 0.75 mg/kg bolus, then
previously administered UFH with
1.75 mg/kg per hour
the addition of 600 mg of
infusion (Class I, LOE: B)
clopidogrel.9 In STEMI patientsundergoing PCI who are at high riskof bleeding, bivalirudinanticoagulation is reasonable.9
December 1, 2009
Appendix 4.
Patient Received Initial Medical
Treatment (With an
Patient Did Not Receive Initial Medical
Anticoagulant and/or
Treatment (With an Anticoagulant
Comments: All Patients to Receive
Fibrinolytic Therapy)
and/or Fibrinolytic Therapy)
ASA (162–325 mg)
IV GP IIb/IIIa planned: target
IV GP IIb/IIIa planned: 50–70 U/kg bolus
ACT 200–250 seconds
to achieve an ACT of 200–250
No IV GP IIb/IIIa planned:
target ACT 250–300
No IV GP IIb/IIIa planned: 70–100 U/kg
seconds for HemoTec,
bolus to achieve target ACT of
300–350 seconds for
250–300 seconds for HemoTec,
Hemochron (Class I, LOE: C)
300–350 seconds for Hemochron(Class I, LOE: C)
ACT indicates activated clotting time; BMS, bare-metal stent; CABG, coronary artery bypass graft; DES, drug-eluting stent; GP, glycoprotein; IV, intravenous; LD,
loading dose; LOE, level of evidence; MACE, major adverse cardiac events; MD, maintenance dose; PCI, percutaneous coronary intervention; STEMI, ST-elevationmyocardial infarction; TIA, transient ischemic attack; and UFH, unfractionated heparin.
*This list is in alphabetical order and is not meant to indicate a particular therapy preference. This drug table does not make recommendations for combinations
of listed drugs. It is only meant to indicate approved dosages if a drug is chosen for a given situation.
†The optimum LD of clopidogrel has not been established. Randomized trials establishing its efficacy and providing data on bleeding risks used an LD of 300 mg
orally followed by a daily oral dose of 75 mg.26,27 Higher oral LDs such as 600 mg or more than 900 mg36 of clopidogrel more rapidly inhibit platelet aggregation andachieve a higher absolute level of inhibition of platelet aggregation, but the additive clinical efficacy and safety of higher oral LD have not been rigorously established.
For post-PCI patients receiving a DES, a daily MD should be given for at least 12 months unless the risk of bleeding outweighs the anticipated net benefit affordedby a thienopyridine. For post-PCI patients receiving a BMS, an MD should be given for a minimum of 1 month28 and ideally up to 12 months (unless the risk of bleedingoutweighs the anticipated net benefit afforded by a thienopyridine; then it should be given for a minimum of 2 weeks). The necessity for giving an LD of clopidogrelbefore PCI is driven by the pharmacokinetics of clopidogrel, for which a period of several hours is required to achieve desired levels of platelet inhibition. Patientswho have a reduced-function CYP2C19 allele have significantly lower levels of the active metabolite of clopidogrel, diminished platelet inhibition, and a higher rateof MACE, including stent thrombosis.53 In STEMI patients taking clopidogrel for whom CABG is planned and can be delayed, it is reasonable to discontinue theclopidogrel to allow for dissipation of the antiplatelet effect, unless the urgency for revascularization and/or the net benefit of clopidogrel outweighs the potential risksof excess bleeding. The period of withdrawal should be at least 5 days in patients receiving clopidogrel.30 Clopidogrel LD after fibrinolytic therapy: For patients givenfibrin- and non–fibrin-specific fibrinolytic drugs who are undergoing PCI within 24 hours, 300 mg; for patients given a fibrin-specific fibrinolytic undergoing PCI aftermore than 24 hours, 300 to 600 mg; for patients given a non–fibrin-specific fibrinolytic undergoing PCI between 24 and 48 hours, 300 mg; for patients given anon–fibrin-specific fibrinolytic undergoing PCI after 48 hours, 300 to 600 mg.
‡Patients weighing ⬍60 kg have an increased exposure to the active metabolite of prasugrel and an increased risk of bleeding on a 10-mg once-daily MD. Consider
lowering the MD to 5 mg in patients who weigh ⬍60 kg. The effectiveness and safety of the 5-mg dose have not been studied prospectively. For post-PCI patientsreceiving a DES, a daily MD should be given for at least 12 and up to 15 months unless the risk of bleeding outweighs the anticipated net benefit afforded by athienopyridine. Do not use prasugrel in patients with active pathological bleeding or a history of TIA or stroke. In patients ⱖ75 years of age, prasugrel is generallynot recommended because of the increased risk of fatal and intracranial bleeding and uncertain benefit, except in high-risk situations (patients with diabetes or ahistory of prior MI) for which its effect appears to be greater and its use may be considered. Do not start prasugrel in patients likely to undergo urgent CABG. Whenpossible, discontinue prasugrel at least 7 days before any surgery. Additional risk factors for bleeding include body weight ⬍60 kg, propensity to bleed, concomitantuse of medications that increase the risk of bleeding (eg, warfarin, heparin, fibrinolytic therapy, or chronic use of nonsteroidal antiinflammatory drugs).
Kushner et al
2009 Focused Updates: STEMI and PCI Guidelines
Appendix 5.
Triage and Transfer for PCI
who is a candidate
Initially seen at a
Initially seen at a
Send to Cath Lab
Initial treatment with
fibrinolytic therapy
reperfusion strategy*
(Class I, LOE: A)
(Class I, LOE: A)
(Class I, LOE: A)
Transfer to a PCI
Transfer to a PCI
Preparatory antithrombotic (anticoagulant
plus antiplatelet) regimen
early diagnostic
(Class IIb, LOE:
angio and possible
C), especially if
(Class IIa, LOE: B)
symptoms persist
High-risk patients
(Class I, LOE: B)
Angio indicates angiography; CABG, coronary artery bypass graft surgery; Cath Lab, catheterization laboratory; LOE, level of evidence; PCI, percutaneous coronary
intervention; and STEMI, ST-elevation myocardial infarction.
Each community and each facility in that community should have an agreed-on plan for how STEMI patients are to be treated that includes which hospitals should
receive STEMI patients from emergency medical services units capable of obtaining diagnostic electrocardiograms, management at the initial receiving hospital, andwritten criteria and agreements for expeditious transfer of patients from non–PCI-capable to PCI-capable facilities. Consideration should be given to initiating apreparatory pharmacological regimen as soon as possible in preparation for and during patient transfer to the catheterization laboratory. The optimal regimen is notyet established, although published studies (see text for details) have used various combinations of the following: anticoagulant, oral antiplatelet agents, intravenousantiplatelet.
*Time since onset of symptoms; risk of STEMI; risks associated with fibrinolytic therapy; time required for transport to a skilled PCI laboratory.
Appendix 6.
Outcomes of PCI Versus CABG for Unprotected Left Main Coronary Artery Disease
Type of Study, Years of Recruitment
Short-Term Results
Long-Term Results
Chieffo et al,141 2006
Cohort, 2002–2004
In-hospital outcomes for PCI versus CABG:
1-Year adjusted ORs for PCI versus CABG:
Death: 0% versus 2.1%; P⫽NS
Death or MI: 0.26; 95% CI 0.078–0.597; P⫽0.0005
MI: 9.3% versus 26.1%; P⫽0.0009
Death, MI, or stroke: 0.385; 95% CI 0.180–0.819;
Stroke: 0% versus 2%; P⫽NS
Revascularization: 4.2; 95% CI 1.486–14.549; P⫽0.005
Lee et al,151 2006
Cohort, 2003–2005
30-Day outcomes for PCI versus CABG:
1-Year follow-up for PCI versus CABG:
Death: 2% versus 5%; P⫽NS
Death: 4% versus 15%; P⫽0.2
MI: 0% versus 2%; P⫽NS
Death, MI, stroke: 4% versus 21%; HR⫽4.4; 95% CI
Stroke: 0% versus 8%; P⫽0.03
Revascularization: 13.3% versus 5.5%; P⫽0.2
versus 2%; P⬍0.01
Palmerini et al,152 2006
Cohort, 2002–2005
30-Day outcomes for PCI versus CABG:
1- to 2-Year follow-up for PCI and CABG:
Death: 3.2% versus 4.5%; P⫽NS
Death: 13.4% versus 12.3%; 95% CI 0.51–1.77;
MI: 4.5% versus 1.9%; P⫽NS
Revascularization: 0.6% versus 0.6%;
MI: 8.3% versus 4.5%; 95% CI 0.21–1.32; P⫽0.17
Revascularization: 2.6% versus 25.5%; 95% CI
Buszman et al,150 2008
Randomized, 2001–2004
30-Day outcomes for PCI versus CABG:
1-Year follow-up for PCI versus CABG:
Death: 0% versus 0%
Death: 2% versus 8%; P⫽NS
MI: 2% versus 4%; P⫽NS
MI: 2% versus 6%; P⫽NS
MACE: 2% versus 14%; 95% CI
Revascularization: 30% versus 10%; 95% CI
MACE: 32% versus 26%; 95% CI 0.85–1.38; P⫽NS
December 1, 2009
Appendix 6.
Type of Study, Years of Recruitment
Short-Term Results
Long-Term Results
Sanmartin et al,154
Cohort, 2000–2005
At 30 days for PCI versus CABG:
At 1 year, for PCI versus CABG:
Death: 2.1% versus 6.1%; P⫽0.17
Death: 5.2% versus 8.4%; P⫽0.37
MI: 0% versus 1.3%; P⫽0.44
versus 9.0%; P⫽0.03
Repeat revascularization: 5.2% versus 0.8%; P⫽0.02Death/MI/stroke/revascularization: 10.4% versus
11.4%; P⫽0.5
Brener et al,156 2008
Cohort with matched CABG controls,
At 3 years, outcomes for PCI versus CABG:
Death: 20% versus 15%; P⫽0.14
Seung et al,139 2008
Matched cohort, 2000–2006
At 3 years, HRs for PCI versus CABG:
Death: 1.18; HR⫽1.18; 95% CI 0.77–1.80; P⫽0.45Death/MI/stroke: 1.10; HR⫽1.10; 95% CI 0.75–1.62;
Revascularization: 4.76; HR⫽4.76; 95% CI
White et al,155 2008
Cohort, 2003–2007
At 30 months, HRs for PCI versus CABG:
Death: 1.93; 95% CI 0.89–4.19; P⫽0.10
Serruys et al,21 2009
Randomized, 2005–2007
At 1 year, HRs for PCI versus CABG:
Death/MI/CVA/revascularization: 15.8 versus 13.7;
CABG indicates coronary artery bypass graft surgery; CI, confidence interval; CVA, cerebrovascular accident; HR, hazard ratio; MACE, major adverse cardiac events;
MI, myocardial infarction; NS, not significant; OR, odds ratio; RR, relative risk; and PCI, percutaneous coronary intervention.
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KEY WORDS: ACCF/AHA practice guidelines 䡲 focused update 䡲
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glycoprotein IIb/IIIa receptor antagonists
Source: http://www.interventor.ru/ru/downloads/AHA-2009-guideline.pdf
ORIGINAL ORIGINAL Non-surgical periodontal therapy for the treatment of chronic periodontitis Terapia periodontal não-cirúrgica no tratamento da periodontite crônica Mari Raquel Botlender TROJAHN1 Robert Carvalho da SILVA2 Júlio César JOLY2 The aim of this split-mouth controlled study was to compare the clinical benefits of administering subgingival 10% Doxycycline (test group)
Prof. Daniel Kraus - Liste des publications, conférences et cours donnés Précis de propriété intellectuelle (avec Nathalie Tissot et Vincent Salvadé), éd. Stämpfli A paraître en 2014 Le droit d'auteur des planificateurs (avec Blaise Carron, Mélanie Krüsi et Yann Férolles), éd. Schulthess (version allemande : 2014 ; version française : 2015)
