PRAGUE, Czech Republic — The antiplatelet agent prasugrel (Effient, Lilly/Daiichi-Sankyo) failed to show noninferiority to clopidogrel (Plavix, Bristol-Myers Squibb) in reducing vascular events among patients with noncardioemboic ischemic stroke, in a new Japanese study.
The PRASTRO-I study, a phase 3 randomized controlled trial, was presented at the recent 3rd European Stroke Organisation Conference (ESOC) 2017 by Kazunori Toyoda, MD, National Cerebral and Cardiovascular Center, Suita-Osaka, Japan.
Professor Toyoda explained that prasugrel, a thienopyridine inhibitor of the platelet P2Y12 receptor, has been widely used for patients with acute coronary syndromes and shows less platelet resistance than clopidogrel, but its effects in stroke patients have not been clarified.
The PRASTRO-I study included 3747 patients younger than age 75 years from 224 Japanese hospitals and between 1 and 26 weeks after an acute noncardioembolic ischemic stroke. They were randomly assigned to receive prasugrel (3.75 mg once daily) or clopidogrel (75 mg once daily) for 96 weeks.
The primary objective was to determine whether prasugrel would be noninferior (below a margin of 1.35) to clopidogrel with respect to the primary composite outcome of ischemic stroke, myocardial infarction, or other vascular death.
Results showed that a primary outcome event occurred in 73 of 1885 (3.9%) patients receiving prasugrel vs 69 of 1862 (3.7%) patients receiving clopidogrel (RR, 1.05; 95% confidence interval [CI], 0.76 – 1.44).
The upper limit of the 95% CI (1.44) was not within the prespecified margin (1.35), so prasugrel could not be considered “noninferior” in this study, Professor Toyoda explained.
However, in the subgroup of patients with large-vessel atherosclerosis or small-vessel occlusion, prasugrel did fulfill the noninferiority criteria, with 3.5% of patients developing the composite vascular endpoint vs 4.3% of those receiving clopidogrel (hazard ratio, 0.81; 95% CI, 0.53 – 1.22).
Any stroke, as a secondary outcome, occurred in 73 patients (3.9%) for both groups (RR, 0.99; 95% CI, 0.72 – 1.36).
A composite safety outcome of life-threatening bleeding, major bleeding, or clinically relevant bleeding occurred in 115 (6.1%) patients receiving prasugrel vs 110 (5.9%) of those receiving clopidogrel (RR, 1.02; 95% CI, 0.79 – 1.33).
Commenting on the study for Medscape Medical News, Alastair Webb, MD, Oxford University, United Kingdom, said, “In cardiology, prasugrel has shown superiority over clopidogrel, but in this study in stroke patients it did not show noninferiority — the confidence intervals were too wide. But the subgroup with large artery disease may have been noninferior.”
“This study won’t change practice, but I think it might lead to more studies maybe in the large-vessel disease group,” Dr Webb said.
The PRASTRO-I study was funded by Daiichi Sankyo.
3rd European Stroke Organisation Conference (ESOC) 2017. Session P24. Presented May 18, 2017.
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