Background: Patients with limited cerebral ischaemia of arterial origin have an annual risk of major vascular events between 4% and 11%. Aspirin reduces this risk by 20% at most. Secondary prevention trials after myocardial infarction indicate that treatment with oral anticoagulants is associated with a risk reduction approximately twice that of treatment with antiplatelet therapy.
Objectives: To compare the efficacy and safety of oral anticoagulants and antiplatelet therapy in the secondary prevention of vascular events after cerebral ischaemia of presumed arterial origin.
Search strategy: We searched the Cochrane Stroke Group Trials Register (searched 16 September 2004). Authors of published trials were contacted for further information and unpublished data.
Selection criteria: Randomised trials examining long-term secondary prevention after recent ischaemic stroke of presumed arterial origin were selected. The oral anticoagulant therapy had to be of specified intensity with warfarin, phenprocoumon or acenocoumarol versus antiplatelet therapy.
Data collection and analysis: Two authors independently selected trials for inclusion, assessed trial quality and extracted data. Subgroup analyses with treatment International Normalized Ratio (INR) 1.4 to 2.8 (low intensity), INR 2.1 to 3.6 (medium intensity) and INR 3.0 to 4.5 (high intensity) were performed.
Main results: Five trials, with 4076 patients were selected. The data do not allow a robust conclusion on whether anticoagulants are more or less efficacious in the prevention of vascular events than antiplatelet therapy (medium intensity anticoagulation relative risk (RR) 0.96, 95% confidence intervals (CI) 0.38 to 2.42; high intensity anticoagulation RR 1.02, 95% CI 0.49 to 2.13). There is no evidence that treatment with low or medium intensity anticoagulation gives a higher bleeding risk than treatment with antiplatelet agents. The relative risk for major bleeding complications for low intensity anticoagulation was 1.27 (95% CI 0.79 to 2.03) and for medium intensity anticoagulation 1.19 (95% CI 0.59 to 2.41). However, it was clear that high intensity oral anticoagulants with INR 3.0 to 4.5 were not safe, because they yielded a higher risk of major bleeding complications (RR 9.0, 95% CI 3.9 to 21).
Authors' conclusions: For secondary prevention of further vascular events after limited ischaemic stroke of arterial origin, there is insufficient evidence to justify the routine use of medium-intensity oral anticoagulants; such treatment should only be used as part of a clinical trial. More intense anticoagulation is not safe and should not be used in this setting. Low-intensity anticoagulation is not likely to be more or less efficacious than aspirin.