• Interventional Techniques & Devices
• Cardiology Clinical Trials
• Myocardial Infarction

• Interventional Techniques & Devices
• Cardiology Clinical Trials
• Myocardial Infarction
• Cardiology

Pretreatment with prasugrel at the time of diagnosis of non-ST-segment elevation (NSTE) acute coronary syndromes (ACS), rather than at the time of percutaneous intervention (PCI), did not reduce ischemic events and increased bleeding, according to results from A Comparison of Prasugrel at the Time of Percutaneous Coronary Intervention or as Pretreatment at the Time of Diagnosis in Patients With Non-ST Elevation Myocardial Infarction (NSTEMI) [ACCOAST; NCT01015287; Montalescot G et al. N Engl J Med 2013]. Gilles Montalescot, MD, PhD, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France, presented results from the study.

Treatment with prasugrel has been shown to be superior to clopidogrel for reducing ischemic events in patients presenting across the spectrum of ACS intended for interventional treatment; however, treatment was only administered at the time of PCI after angiography was completed [Wiviott SD et al. N Engl J Med 2007]. ACCOAST was a randomized, double-blind, event-driven study to evaluate the administration of prasugrel, a P2Y12 antagonist, at the time of diagnosis (pretreatment) compared with after coronary angiography if PCI was indicated as previously studied. A total of 4033 patients with NSTEMI scheduled for catheterization within 2 to 48 hours were randomized.

The primary composite endpoint was the first occurrence of death from cardiovascular causes, MI, stroke, urgent revascularization, or glycoprotein IIB/IIIa inhibitor rescue therapy (glycoprotein IIB/IIIa bailout) through Day 7 [Montalescot G et al. Am Heart J 2011]. Safety endpoints were major and minor bleeding risks according to TIMI criteria.

Patients in the pretreatment group received 30 mg of prasugrel at the time of diagnosis and if angiography confirmed an indication for PCI, an additional 30 mg of prasugrel was administered. Patients in the control group received placebo initially and a 60-mg prasugrel dose was administered following angiography in patients for whom PCI was indicated and performed.

From randomization to Day 7, there was no difference in the primary endpoint with prasugrel pretreatment compared with prasugrel after angiography (HR with pretreatment, 1.02; 95% CI, 0.84 to 1.25; p=0.81). However, there was a significant, nearly 2-fold increase in the rate of TIMI major bleeding in patients receiving prasugrel pretreatment (HR, 1.90; 95% CI, 1.19 to 3.02; p=0.006). The rate of life-threatening bleeding unrelated to coronary artery bypass graft was increased by a factor of 6. Among the 69% of patients who underwent PCI, pretreatment with prasugrel reduced death from cardiovascular causes, MI, stroke, urgent revascularization, or glycoprotein IIB/IIIa inhibitor rescue therapy; however, the rate of TIMI major bleeding at 7 days was significantly increased.

Overall, ACCOAST showed an increased risk of bleeding and demonstrated no benefits with prasugrel pretreatment prior to angiography in patients with NSTEMI, and Prof. Montalescot noted that a re-examination of antiplatelet pretreatment strategies in patients with NSTEMI is necessary.

• © 2013 MD Conference Express®