Pretreatment with Prasugrel Before PCI Is Problematic

Despite limited data regarding the timing of antiplatelet administration, clopidogrel pretreatment in patients with acute coronary syndromes who are scheduled for percutaneous coronary intervention (PCI) has not only become routine but is often extended to newer oral P2Y₁₂ platelet inhibitors. In the manufacturer-funded ACCOAST trial, investigators randomly assigned 4033 patients (mean age 64, 28% women) with non-ST-segment-elevation myocardial infarction (MI) to receive aspirin plus either 30 mg of prasugrel or placebo 2 to 48 hours before angiography. Patients who underwent PCI (68.7%, 43% radial access) received an additional 30 mg (pretreatment group) or 60 mg (control group) of prasugrel immediately before the intervention (mean, 4.3 hours after initial loading dose). The trial was stopped early because of excess bleeding in the pretreatment group, although the number of primary-outcome events had nearly reached the protocol-defined stopping point (398 of 400 planned).

At 7 days, the rate of the primary efficacy endpoint — a composite of cardiovascular death, MI, stroke, urgent revascularization, and glycoprotein IIb/IIIa-inhibitor rescue therapy — did not differ significantly between the two groups (10.0% vs. 9.8%). However, the rate of thrombolysis in MI major bleeding episodes through day 7 was significantly higher with than without pretreatment (2.6% vs. 1.4%). At 30 days, the early results persisted in the whole cohort as well as in prespecified subgroups.