CLINICAL QUESTION: Should we use warfarin or aspirin to prevent stroke in patients with nonvalvular atrial fibrillation?
BACKGROUND: Patients with atrial fibrillation have a substantial risk of stroke, but the best medication for anticoagulation remains unclear. This meta-analysis compared the safety and effectiveness of warfarin and aspirin in preventing stroke in patients with nonvalvular atrial fibrillation.
POPULATION STUDIED: This paper combined the results of 16 randomized-controlled trials from Europe and North America of 9874 patients with nonvalvular atrial fibrillation. The mean age of subjects was 69 to 71 years, 29% to 38% were women, 45% had hypertension, and 20% to 40% had a previous stroke or transient ischemic attack (TIA). International normalized ratio targets in most studies were 2 to 3 or 2 to 3.5; aspirin dosages ranged from 50 mg per day to 1300 mg per day.
STUDY DESIGN AND VALIDITY: The authors of this meta-analysis reviewed published randomized trials found through OVID and MEDLINE (1966-1999) and by inquiries to the Cochrane Collaboration Stroke Review Group and the Antithrombotic Trialists Collaboration. Studies of valvular atrial fibrillation were excluded. Primary (those that included patients without previous stroke) and secondary (those that included patients with previous stroke or TIA) prevention trials were included. Trials reporting results for subgroups of patients with atrial fibrillation were included, as were nonblinded trials. Two reviewers extracted information on exposure and outcomes by intention-to-treat analysis; homogeneity was tested for each comparison. This was a well-done meta-analysis. Its strengths included the limitation to randomized-controlled trials and the use of independent reviewers; weaknesses included the lack of assessment of study quality, inconsistent reporting of tests for homogeneity, and the lack of analysis of confounders such as risks for hemorrhage, other risks for strokes, or amount of medication. Important outcomes not addressed include cost, patient acceptability, functional status, and quality of life.
OUTCOME MEASURED: The primary outcome reported was the occurrence of all strokes (hemorrhagic and ischemic) presented as relative risk reduction (RRD), absolute risk reduction (ARR) and number needed to treat (NNT) for primary and secondary prevention. Other outcomes included were occurrence of ischemic stroke, intracranial hemorrhage, all-cause mortality, and major extracranial bleeding.
RESULTS: The mean follow-up of patients was 1.7 years. Treatment with adjusted-dose warfarin was superior to placebo for all trials, yielding a 62% RRD (95% confidence interval [CI], 48% - 72%). In patients without a history of stroke or TIA, warfarin produced an ARR of 2.7% (NNT = 37). For secondary prevention, 12 patients needed to be treated to prevent another significant event from occurring (ARR = 2.7%). Of those patients, 60 had to be treated to prevent one death of any cause (ARR = 2.7%).
This meta-analysis provides good evidence that adjusted-dose warfarin is superior to aspirin for stroke prevention in patients with nonvalvular atrial fibrillation. The magnitude of this benefit varies with the risk for stroke. Patients who are at high risk (those with previous stroke or TIA or secondary prevention) have the most to gain from treatment with warfarin compared with aspirin. For patients with a lower risk of stroke (primary prevention), the risks of therapy with warfarin begin to outweigh the benefits.1