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CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY

The Efficacy and Safety of Prasugrel With and Without a Glycoprotein IIb/IIIa Inhibitor in Patients With Acute Coronary Syndromes Undergoing Percutaneous Intervention

A TRITON–TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis In Myocardial Infarction 38) Analysis

Michelle O'Donoghue, MD^_*,_*, Elliott M. Antman, MD^_*, Eugene Braunwald, MD^_*, Sabina A. Murphy, MPH^_*, P. Gabriel Steg, MD, Ariel Finkelstein, MD^||, William F. Penny, MD, Viliam Fridrich, MD, Carolyn H. McCabe, BSc^_*, Marc S. Sabatine, MD, MPH^_* and Stephen D. Wiviott, MD^_*

^_* TIMI Study Group, Brigham and Women's Hospital, Boston, Massachusetts
INSERM U-698, Université Paris 7, AP-HP, Paris, France
University of California, San Diego/VA Medical Center, San Diego, California
Slovak Institute of Cardiovascular Disease, Bratislava, Slovakia
^|| Tel-Aviv Medical Center, Tel-Aviv, Israel

Manuscript received February 13, 2009; revised manuscript received May 4, 2009, accepted May 12, 2009.

^_* Reprint requests and correspondence: Dr. Michelle O'Donoghue, TIMI Study Group, Brigham and Women's Hospital, 350 Longwood Avenue, 1st Floor, Boston, Massachusetts 02115 (Email: modonoghue{at}partners.org).

Objectives: We evaluated the efficacy and safety of prasugrel and clopidogrel in the setting of a glycoprotein (GP) IIb/IIIa inhibitor.

Background: Prasugrel reduced cardiovascular events as compared with clopidogrel in TRITON–TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction 38) but with increased bleeding.

Methods: Researchers in the TRITON–TIMI 38 randomized 13,608 subjects with acute coronary syndrome undergoing percutaneous coronary intervention to prasugrel versus clopidogrel. The use of a GP IIb/IIIa inhibitor was at the physician's discretion. For the current analysis, end points were examined at 30 days and were stratified by use of a GP IIb/IIIa inhibitor.

Results: A total of 7,414 subjects (54.5%) received a GP IIb/IIIa inhibitor during their index hospitalization. There was a consistent benefit of prasugrel over clopidogrel for reducing cardiovascular death, myocardial infarction, or stroke in patients who did (hazard ratio: 0.76; 95% confidence interval: 0.64 to 0.90) or did not receive a GP IIb/IIIa inhibitor (hazard ratio: 0.78; 95% confidence interval: 0.63 to 0.97, p_interaction = 0.83). Prasugrel significantly reduced myocardial infarction, urgent revascularization, and stent thrombosis irrespective of GP IIb/IIIa inhibitor use. Although subjects treated with a GP IIb/IIIa inhibitor had greater rates of bleeding, the risk of Thrombolysis in Myocardial Infarction major or minor bleeding with prasugrel versus clopidogrel was not significantly different in patients who were or were not treated with GP IIb/IIIa inhibitor (p_interaction = 0.19).

Conclusions: Prasugrel significantly reduces the risk of cardiovascular events in patients with acute coronary syndromes after percutaneous coronary intervention regardless of whether or not a GP IIb/IIIa inhibitor is used. The use of a GP IIb/IIIa inhibitor does not accentuate the relative risk of bleeding with prasugrel as compared with clopidogrel.

Key Words: prasugrel • clopidogrel • thienopyridine • glycoprotein IIb/IIIa inhibitor • platelets • acute coronary syndrome • percutaneous intervention

Abbreviations and Acronyms   ACS = acute coronary syndrome   CABG = coronary artery bypass graft surgery   CI = confidence interval   CV = cardiovascular   GP = glycoprotein   HR = hazard ratio   MI = myocardial infarction   NSTEMI = non–ST-segment elevation myocardial infarction   PCI = percutaneous coronary intervention   STEMI = ST-segment elevation myocardial infarction   TIMI = Thrombolysis In Myocardial Infarction   UA = unstable angina

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