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(Circulation. 2009;119:2758-2764.)
© 2009 American Heart Association, Inc.

Coronary Heart Disease

Effect of the Novel Thienopyridine Prasugrel Compared With Clopidogrel on Spontaneous and Procedural Myocardial Infarction in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction 38

An Application of the Classification System From the Universal Definition of Myocardial Infarction

David A. Morrow, MD, MPH; Stephen D. Wiviott, MD; Harvey D. White, DSc; Jose C. Nicolau, MD; Ezio Bramucci, MD; Sabina A. Murphy, MPH; Marc P. Bonaca, MD; Christian T. Ruff, MD; Benjamin M. Scirica, MD, MPH; Carolyn H. McCabe, BS; Elliott M. Antman, MD; Eugene Braunwald, MD

From the TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Boston, Mass (D.A.M., S.D.W., S.A.M., M.P.B., C.T.R., B.M.S., C.H.M., E.M.A., E. Braunwald); Auckland City Hospital, Auckland, New Zealand (H.D.W.); Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil (J.C.N.); and Division of Cardiology, IRCCS Policlinico San Matteo, Pavia, Italy (E. Bramucci).

Correspondence to David A. Morrow, MD, MPH, TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail dmorrow{at}partners.org

Received November 4, 2008; accepted March 12, 2009.

Background— Prasugrel is a novel thienopyridine that reduces new or recurrent myocardial infarctions (MIs) compared with clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention. This effect must be balanced against an increased bleeding risk. We aimed to characterize the effect of prasugrel with respect to the type, size, and timing of MI using the universal classification of MI.

Methods and Results— We studied 13 608 patients with acute coronary syndrome undergoing percutaneous coronary intervention randomized to prasugrel or clopidogrel and treated for 6 to 15 months in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction (TRITON-TIMI 38). Each MI underwent supplemental classification as spontaneous, secondary, or sudden cardiac death (types 1, 2, and 3) or procedure related (Types 4 and 5) and examined events occurring early and after 30 days. Prasugrel significantly reduced the overall risk of MI (7.4% versus 9.7%; hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.67 to 0.85; P<0.0001). This benefit was present for procedure-related MIs (4.9% versus 6.4%; HR, 0.76; 95% CI, 0.66 to 0.88; P=0.0002) and nonprocedural (type 1, 2, or 3) MIs (2.8% versus 3.7%; HR, 0.72; 95% CI, 0.59 to 0.88; P=0.0013) and consistently across MI size, including MIs with a biomarker peak 5 times the reference limit (HR. 0.74; 95% CI, 0.64 to 0.86; P=0.0001). In landmark analyses starting at 30 days, patients treated with prasugrel had a lower risk of any MI (2.9% versus 3.7%; HR, 0.77; P=0.014), including nonprocedural MI (2.3% versus 3.1%; HR, 0.74; 95% CI, 0.60 to 0.92; P=0.0069).

Conclusion— Treatment with prasugrel compared with clopidogrel for up to 15 months in patients with acute coronary syndrome undergoing percutaneous coronary intervention significantly reduces the risk of MIs that are procedure related and spontaneous and those that are small and large, including new MIs occurring during maintenance therapy.

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