A RANDOMIZED TRIAL OF ANTICOAGULANTS VERSUS ASPIRIN AFTER CEREBRAL-ISCHEMIA OF PRESUMED ARTERIAL ORIGIN

Aspirin is only modestly effective in the secondary prevention after c erebral ischemia Studies in other vascular disorders suggest that anti coagulant drugs in patients with cerebral ischemia of presumed arteria l (noncardiac) origin might be more effective. The aim of the Stroke P revention in Reversible Ischemia Trial (SPIRIT) therefore was to compa re the efficacy and safety of 30 mg aspirin daily and oral anticoagula tion (international normalized ratio [INR] 3.0-4.5), Patients referred to a neurologist in one of 58 collaborating centers because of a tran sient ischemic attack or minor ischemic stroke (Rankin grade less than or equal to 3) were eligible. Randomization was concealed, treatment assignment was open, and assessment of outcome events was masked. The primary measure of outcome was the composite event ''death from all va scular causes, nonfatal stroke, nonfatal myocardial infarction, or non fatal major bleeding complication.'' The trial was stopped at the firs t interim analysis. A total of 1,316 patients participated; their mean follow-up was 14 months. There was an excess of the primary outcome e vent in the anticoagulated group (81 of 651) versus 36 of 665 in the a spirin group (hazard ratio, 2.3; 95% confidence interval [CI], 1.6-3.5 ). This excess could be attributed to 53 major bleeding complications (27 intracranial; 17 fatal) during anticoagulant therapy versus 6 on a spirin (3 intracranial; 1 fatal). The bleeding incidence increased by a factor of 1.43 (95% CI, 0.96-2.13) for each 0.5 unit increase of the achieved INR. Anticoagulant therapy with an INR range of 3.0 to 4.5 i n patients after cerebral ischemia of presumed arterial origin is not safe. The efficacy of a lower intensity anticoagulation regimen remain s to be determined.