Clopidogrel Two Doses Comparative 1-Year Assessment of Safety and Efficacy (COMPASS) Study in Japanese Patients with Ischemic Stroke

<b><i>Background:</i></b> Clopidogrel 75 mg once daily is licensed in Japan for the prevention of recurrent ischemic cerebrovascular events in adults as the usual dosage. However, a lower dose (50 mg) is an option in patients at an increased risk of bleeding depending on age, body weight and symptoms. This study compared the safety of both 75- and 50-mg doses of clopidogrel in patients with noncardioembolic ischemic stroke. <b><i>Methods:</i></b> This was a double-blind, double-dummy postmarketing clinical trial carried out across 118 Japanese institutions. Patients with an episode of noncardioembolic ischemic stroke at least 8 days prior to randomization, who were aged <75 years or had a body weight >50 kg were randomized to 50 or 75 mg clopidogrel once daily for 52 weeks. The primary endpoint was the incidence of bleeding adverse events. The secondary safety endpoints included the incidence of serious adverse events, serious bleeding adverse events and other prespecified adverse events. The secondary efficacy endpoint was the incidence of vascular events, including ischemic stroke, myocardial infarction, and peripheral artery disease. <b><i>Results:</i></b> A total of 1,110 patients were randomized to clopidogrel 50 mg (n = 558) or 75 mg (n = 552). No significant difference between the groups was detected in the incidence of bleeding adverse events, which was 14.0 and 16.5% in the clopidogrel 50- and 75-mg groups, respectively (hazard ratio = 0.831, 95% CI = 0.615–1.124, p = 0.2274). Additionally, there was no statistical difference with respect to any of the secondary safety endpoints. No significant difference between the groups was detected in the incidence of serious adverse events, which was 8.6 and 9.5% in the clopidogrel 50- and 75-mg groups, respectively (hazard ratio = 0.877, 95% CI = 0.597–1.289, p = 0.5035), and there was no significant difference between the groups in the incidence of serious bleeding events, which was 1.7 and 1.5% in the clopidogrel 50- and 75-mg groups, respectively (hazard ratio = 1.240, 95% CI = 0.489–3.142, p = 0.6496). The percentages of intracranial hemorrhage in the 50- and 75-mg groups were 0.18% (1/558) and 0.18% (1/552), respectively. The cumulative incidence of vascular events was somewhat lower in the 75-mg group, but was not statistically different (2.6 vs. 3.8%; p = 0.4118). <b><i>Conclusions:</i></b> Clopidogrel 75 mg provides a clinically acceptable safety profile and suggests better clinical benefit as compared to clopidogrel 50 mg for the secondary prevention of ischemic stroke in Japanese patients who are <75 years old with a body weight >50 kg, considering the balance of safety and efficacy on this trial.