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Pretreatment with Prasugrel Before PCI Is Problematic

Summary and Comment |
September 1, 2013

Pretreatment with Prasugrel Before PCI Is Problematic

  1. Beat J. Meyer, MD

In the ACCOAST trial, giving the drug before coronary angiography was not more efficacious than just-in-time administration and significantly increased bleeding.

  1. Beat J. Meyer, MD

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.

Comment

In this study, pretreatment with aspirin and prasugrel in patients with non-ST-segment-elevation myocardial infarction did not prevent thrombotic events; indeed, pretreatment significantly increased bleeding risk. Given its rapid onset of action, prasugrel is effective when administered after the coronary anatomy has been defined. This is a particular advantage in patients whose angiographic findings necessitate coronary artery bypass grafting — because no pretreatment is necessary, surgery need not be delayed. Current guidelines should be modified accordingly.

To join a discussion of these findings, read John Ryan, Rick Lange, and David Hillis's interview with Dr. Montalescot on CardioExchange, an online community hosted by the New England Journal of Medicine and NEJM Journal Watch and dedicated to improving cardiac patient care. Membership is free for medical professionals.

  • Disclosures for Beat J. Meyer, MD at time of publication Leadership positions in professional societies CentraMed Organization (President)

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