A RANDOMIZED, BLINDED, TRIAL OF CLOPIDOGREL VERSUS ASPIRIN IN PATIENTS AT RISK OF ISCHEMIC EVENTS (CAPRIE)

Background Many clinical trials have evaluated the benefit of long-ter m use of antiplatelet drugs in reducing the risk of clinical thromboti c events. Aspirin and ticlopidine have been shown to be effective, but both have potentially serious adverse effects. Clopidogrel, a new thi enopyridine derivative similar to ticlopidine, is an inhibitor of plat elet aggregation induced by adenosine diphosphate. Methods CAPRIE was a randomised, blinded, international trial designed to assess the rela tive efficacy of clopidogrel (75 mg once daily) and aspirin (325 mg on ce daily) in reducing the risk of a composite outcome cluster of ischa emic stroke, myocardial infarction, or vascular death; their relative safety was also assessed. The population studied comprised subgroups o f patients with atherosclerotic Vascular disease manifested as either recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease. Patients were followed for 1 to 3 years. Findings 19 185 patients, with more than 6300 in each of the clinical subgroups, were recruited over 3 years, with a mean follow-up of 1 . 9 1 years. There were 1960 first events included in the outcome cluster on which an intention-to-treat analysis showed that patients treated w ith clopidogrel had an annual 5 . 32% risk of ischaemic stroke, myocar dial infarction, or vascular death compared with 5 . 83% with aspirin. These rates reflect a statisticaly significant (p=0 . 043) relative-r isk reduction of 8 . 7% in favour of clopidogrel (95% CI 0 . 3-16 . 5) . Corresponding on-treatment analysis yielded a relative-risk reductio n of 9 . 4%. There were no major differences in terms of safety. Repor ted adverse experiences in the clopidogrel and aspirin groups judged t o be severe included rash (0 . 26% vs 0 . 10%), diarrhoea (0 . 23% vs 0 . 11%), upper gastrointestinal discomfort (0 . 97% vs 1 . 22%), intr acranial haemorrhage (0 . 33% vs 0 . 47%), and gastrointestinal haemor rhage (0 . 52% vs 0 . 72%), respectively. There were ten (0 . 10%) pat ients in the clopidogrel group with significant reductions in neutroph ils (<1 . 2 X 10(9)/L) and 16 (0 . 17%) in the aspirin group. Interpre tation Long-term administration of clopidogrel to patients with athero sclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction, or vascu lar death. The overall safety profile of clopidogrel is at least as go od as that of medium-dose aspirin.