A Randomized Trial of Prasugrel Versus Clopidogrel

Study Questions:

What is the safety and efficacy of prasugrel as compared with clopidogrel in patients with high on-treatment platelet reactivity (HTPR) after elective percutaneous coronary intervention (PCI)?


The authors enrolled patients who had HTPR on clopidogrel after undergoing PCI with drug-eluting stents for stable coronary artery disease. HTPR was defined as >208 P2Y12 reaction units [PRU] by the VerifyNow test. A total of 423 patients were randomly assigned to either prasugrel 10 mg daily or clopidogrel 75 mg daily. Platelet reactivity of the patients on the study drug was reassessed at 3 and 6 months. The study was stopped prematurely for futility.


Among the 212 patients assigned to prasugrel, PRU decreased from a median of 245 to 80 at 3 months, whereas in 211 patients assigned to clopidogrel, PRU decreased from 249 to 241 (p < 0.001 vs. prasugrel). There was no difference in the primary efficacy endpoint of cardiac death or myocardial infarction at 6 months (none on prasugrel vs. one on clopidogrel). The primary safety endpoint of non–coronary artery bypass graft Thrombolysis in Myocardial Infarction major bleeding at 6 months occurred in three patients (1.4%) on prasugrel versus one (0.5%) on clopidogrel.


The authors concluded that switching from clopidogrel to prasugrel in patients with HTPR was associated with effective platelet inhibition. Despite the enhanced platelet inhibition, there was no difference in ischemic events, which were low in both arms.


This study failed to demonstrate a clinical benefit of better platelet inhibition with prasugrel in patients with HTPR after elective PCI. Combined with the results of the GRAVITAS trial, these findings question the utility of using platelet function assays to guide antiplatelet therapy after elective PCI. Furthermore, the ischemic event rates in this population were very low in patients who were treated with clopidogrel, and it should remain the thienopyridine of choice in patients undergoing elective PCI.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Aortic Surgery, Interventions and Coronary Artery Disease

Keywords: Coronary Artery Disease, Myocardial Infarction, Platelet Aggregation Inhibitors, Drug-Eluting Stents, Thiophenes, Pyridines, Medical Futility, Ticlopidine, Piperazines, Blood Platelets, Coronary Artery Bypass, Percutaneous Coronary Intervention

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