Abstract
BACKGROUND: Peripheral arterial disease (PAD) has been recognized as an independent risk factor for vascular events and contributes to an adverse prognosis. Long-term administration of clopidogrel is recommended to prevent atherothrombotic events for patients with established PAD. We investigated the benefits of clopidogrel treatment in Japanese patients with PAD. MATERIALS AND METHODS: COOPER (Clopidogrel for atherOthrombOtic event management in patients with PERipheral arterial disease) was a multicenter, randomized, double-blind study to evaluate the safety and efficacy of clopidogrel (75 mg/day) compared to ticlopidine (200 mg/day) in Japanese patients with PAD. The primary endpoint was the cumulative incidence of "safety events of interest" comprising clinically significant bleeding, blood disorders, hepatic dysfunction and other serious adverse events up to 12 weeks. The other safety events and vascular events were also assessed. Patients were followed up to 52 weeks. RESULTS: A total of 431 patients with PAD were randomly assigned to receive either clopidogrel or ticlopidine. The cumulative incidences of "safety events of interest" at 12 weeks were 2.4% and 13.6% of patients who received clopidogrel and ticlopidine, respectively (adjusted hazard ratio, 0.161; 95% confidence interval, 0.062 to 0.416; p <0.0001). Bleeding and vascular events were similar in both groups. CONCLUSION: Clopidogrel demonstrated a favorable benefit/risk profile than ticlopidine in Japanese patients with PAD. ( TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT00862420).