Eight studies were included in the review, of which five were primary prevention placebo-controlled studies (total number of participants not stated), 1 study evaluated secondary prevention of stroke (1,007 participants), 1 study compared warfarin and aspirin (1,100 participants), and 1 study evaluated warfarin in combination with aspirin (1,044 participants).
The risk of developing stroke is heterogeneous and increases with each decade above 65 years; history of high blood pressure, diabetes mellitus, previous transient ischemic attack, or stroke; poor ventricular function; and in women older than 75 years.
For patients younger than 65 years, without risk factors, and not receiving antithrombotic therapy, the risk of stroke is 1% per year; those without risk factors between the ages of 65 and 75 years have a risk of 1.1% per year if taking warfarin and 1.4% per year if taking aspirin.
For all other patients, stroke risk is reduced from an untreated rate of between 4.3% per year and more than 12% per year to a rate of 1.2% per year to 4% per year with warfarin use.
In the primary prevention studies warfarin reduced the risk of stroke by 68% (4.5% to 1.4% per year) with virtually no increase in the frequency of major bleeding (the rates were 1.2%, 1.0%, and 1.0% per year for warfarin, aspirin and placebo groups respectively.
In the secondary study, warfarin reduced the risk of stroke by 66% (12% to 4% per year). Among all patients assigned to aspirin, the incidence of outcome events was 15% per year compared with 19% per year among the patients receiving placebo. The incidence of major bleeding complications was low in this study: 2.8% per year in the anti-coagulant group, 0.9% per year in the aspirin group, and 0.7% in the placebo group. Fatal intracerebral hemorrhage occurred in 3 patients: 1 in the placebo and 2 in the aspirin group.
In the warfarin versus aspirin study, the primary event rate was 1.3% per year with warfarin and 1.9% per year with aspirin (RR = 0.67; p = 0.24). Patients in this study (over the age of 75 years) were found to have a substantial risk of thromboembolism during aspirin therapy (4.8% per year). Warfarin reduced the risk to 3.6% per year (RR = 0.73; p = 0.39).
In the warfarin and aspirin in combination study, the study was terminated after a mean follow-up of 1.1 years when the rate of ischemic stroke and systemic embolisation in the combination therapy group was 7.9% per year compared with 1.9% per year in the dose- adjusted group (p < 0.001). The rates of major bleeding were similar in both groups.