The noninferiority of prasugrel 3.75 mg/day to clopidogrel 75 mg/day for the prevention of recurrent ischemic stroke, myocardial infarction, and death from other vascular causes could not be confirmed in a population of Japanese patients who had experienced a noncardioembolic stroke. A first-of-its kind, phase 3, randomized, double-blind trial (PRASTRO-I) on the subject was conducted, with the results published in the Lancet Neurology.
Patients between 20 and 74 years of age who had experienced a noncardioembolic stroke in the prior 1 to 26 weeks were recruited from a total of 224 hospitals in Japan. All participants were randomly assigned in a 1:1 ratio to receive clopidogrel 75 mg/day or prasugrel 3.75 mg/day administered orally for 96 to 104 weeks.
Randomization of the participants was stratified based on stroke subtype. Patients, investigators, and funders were all masked to treatment allocation.
The primary study endpoint was the combined incidence of ischemic stroke (both fatal and nonfatal), myocardial infarction, and death from other vascular causes in the intention-to-treat population. The safety endpoint was the incidence of bleeding events, which included life-threatening bleeding, major bleeding, and clinically relevant bleeding.
Study participants were recruited from September 1, 2011, through June 12, 2015. A total of 3747 patients were enrolled, of whom 797 were women. The mean age of the participants was 62.1±8.5 years.
Of the participants, 1885 were treated with prasugrel and 1862 were treated with clopidogrel. Overall, 3.9% (73 of 1885) of patients in the prasugrel group and 3.7% (69 of 1862) of those in the clopidogrel group achieved the primary endpoint (risk ratio, 1.05; 95% CI, 0.76-1.44).
In addition, the incidence of bleeding events did not differ significantly between the 2 treatment groups, with life-threatening bleeding reported in 1.0% (18 of 1885) of those in the prasugrel group and 1.2% (23 of 1862) of patients in the clopidogrel group (hazard ratio, 0.77; 95% CI, 0.41-1.42).
The investigators concluded that by examining the safety and efficacy of prasugrel and clopidogrel for each stroke subtype, it is hoped that useful information will be provided to help guide clinicians in the selection of an appropriate antiplatelet therapy for their patients who experience a noncardioembolic stroke.
Ogawa A, Toyoda K, Kitagawa K, et al; PRASTRO-I Study Group. Comparison of prasugrel and clopidogrel in patients with non-cardioembolic ischaemic stroke: a phase 3, randomised, non-inferiority trial (PRASTRO-I). Lancet Neurol. 2019;18(3):238-247.