Antithrombotics in Acute Coronary Syndromes
Marc P. Bonaca, MD*,
Philippe Gabriel Steg, MD ,
Laurent J. Feldman, MD,
John F. Canales, MD ,
James J. Ferguson, MD, ,
Lars Wallentin, MD, PhD||,
Robert M. Califf, MD¶,
Robert A. Harrington, MD¶ and
Robert P. Giugliano, MD, SM*,*
* TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts
Centre Hospitalier Bichat-Claude Bernard, Université Paris VII–Denis Diderot, Paris, France
Texas Heart Institute at St. Luke's Episcopal Hospital, Baylor College of Medicine, Houston, Texas
The University of Texas Health Science Center at Houston, Houston, Texas
|| Uppsala Clinical Research Centre at Uppsala University, Uppsala, Sweden
¶ Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
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Figure 1 Major Trial Findings in FINESSE and On-TIME 2
(A) Major findings in the FINESSE trial (16). The rates of complete (>70%) ST-segment resolution at 60 to 90 min, primary composite (all-cause mortality, ventricular fibrillation >48 h, cardiogenic shock, congestive heart failure) through 90 days, Thrombolysis In Myocardial Infarction (TIMI) major bleeding, or TIMI minor bleeding were not significantly different between patients randomized to abciximab facilitated percutaneous coronary intervention (PCI) versus primary PCI. Abciximab did increase the combined rate of nonintracranial major or minor bleeding. (B) Major findings in the On-TIME 2 trial (17). The rate of complete ST-resolution after PCI was greater, and clinical composite of death, recurrent myocardial infarction, urgent target vessel revascularization, or blinded bail-out use of tirofiban at 30 days was lower in the tirofiban arm. There was no significant difference in TIMI major bleeding, TIMI minor bleeding, or net clinical outcome (death, recurrent myocardial infarction, urgent target vessel revascularization, or major bleeding). NS = not significant.
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Figure 2 Trials of LMWHs
(A) Trials with LMWHs in ACS. Shown at the top are older clinical trials in STEMI (left) and UA/NSTEMI (right). More recent data in both STEMI and UA/NSTEMI and very recent data from CREATE (Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment Evaluation) and ExTRACT–TIMI 25 (in STEMI) and OASIS 5 (discussed in the Factor Xa inhibitors section, where enoxaparin was the control arm) have provided additional guidance for the use of LMWH in ACS. (B) Studies of LMWH in patients undergoing PCI. Shown at the top (light background) are older observational studies of LMWH as procedural anticoagulation (left) and in patients transitioned to the laboratory (right), most frequently in previous ACS trials such as ESSENCE (Efficacy and Safety of Subcutaneous ENoxaparin in Non-Q-Wave Coronary Events), TIMI 11B, and FRISC II (FRagmin and Fast Revascularisation during InStability in Coronary artery disease). More recent randomized data for procedural anticoagulation and from large contemporary ACS trials where LMWH patients were brought to the catheterization laboratory, as well as very recent data from STEEPLE (for procedural anticoagulation) and ExTRACT–TIMI 25 and OASIS 5 (where enoxaparin patients were transitioned to the catheterization laboratory) have provided useful new information on the use of LMWH in the catheterization laboratory. ACS = acute coronary syndrome; LMWH = low molecular weight heparins; NSTEMI = non–ST-segment elevation myocardial infarction; UA = unstable angina; other abbreviations as in Figure 1.
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Figure 3 Antithrombotic Protocol Used in SYNERGY
The SYNERGY trial (63) used a pre-specified protocol to transition patients in a controlled fashion to/from UFH and LMWH. UFH = unfractionated heparin; other abbreviations as in Figure 2.
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Figure 4 Main Results From HORIZONS-AMI
In HORIZONS-AMI (78), bivalirudin (Bival) was reduced the primary end point of net adverse clinical events (composite of major non-coronary artery bypass grafting (CABG) bleeding and major adverse cardiovascular events) and major non-coronary artery bypassing grafting (CABG) bleeding compared to heparin and glycoprotein IIb/IIIa inhibitor (GPI). There was no difference in the composite of major adverse cardiovascular events (composite of death, reinfarction [ReMI], target vessel revascularization for ischemia [TVR], or stroke).
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