On July 10, 2009, the Food and Drug Administration (FDA) approved prasugrel for use in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI).1 In the pivotal clinical trial on which this decision was based (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction 38 [TRITON–TIMI 38]), prasugrel reduced the primary composite end point of cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke by 19% compared with clopidogrel.2 The benefit was driven primarily by nonfatal MI, including clinically silent biomarker elevations.3,4 The majority of the benefit occurred in the first 30 days of follow-up.3,4 Despite the exclusion of patients at high risk of bleeding, prasugrel was nevertheless associated with an overall 31% increase in bleeding, a 52% increase in life-threatening bleeding, and a 318% increase in fatal bleeding. Bleeding, unlike treatment benefit, appeared to persist throughout follow-up.3,4 The prasugrel label was restricted to a claim for prevention of thrombotic cardiovascular events driven primarily by nonfatal MI and boxed warnings added for bleeding risk.1 Given the issues with the dose and timing of clopidogrel administration, a superiority claim over clopidogrel was not allowed.1
Kaul S, Diamond GA. Prasugrel and Cancer: An Uncertain Association or a Credible Risk That Meaningfully Alters the Benefit-Risk Balance. Arch Intern Med. 2010;170(12):1010–1012. doi:10.1001/archinternmed.2010.139
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