Background Previous studies have shown that secondary prophylaxis of non-embolic stroke remains challenging. Randomized controlled trials (RCTs) evaluating warfarin with or without aspirin to prevent stroke have yielded mixed results. We conducted a meta-analysis of RCTs to evaluate the efficacy of warfarin (with and without aspirin) in patients with coronary artery disease (CAD) or ischemic stroke/ transient ischemic attack (TIA).
Methods We searched 6 electronic databases published from 1980–2014. RCTs reporting the benefits (reduced incidence of stroke) and risks (mortality, intracranial bleeds, major and minor bleeds) of warfarin (with and without aspirin) therapy were included. Trials were stratified by intensity of the therapeutic international normalized ratio (INR): low (INR<2), intermediate (INR 2–3) and high (INR>3). Risk ratios (RRs) were pooled using random-effects models.
Results Twenty-five RCTs (30,939 patients) met our inclusion criteria. Intermediate intensity warfarin with aspirin compared with aspirin alone significantly reduced the risk of secondary strokes [RR 0.48, 95% confidence interval (CI) 0.29–0.80], but increased the risk of major bleeding (RR 2.54, CI 1.70–3.79); there were no significant differences in mortality (RR 1.00, CI 0.80–1.25) and intracranial bleeding (RR 3.03, CI 0.48–19.20). Intermediate intensity warfarin without aspirin compared with aspirin alone, significantly increased major bleeding (RR 2.11, CI 1.45–3.06); there were no significant differences for stroke (RR 0.84, CI 0.66–1.08), mortality (RR1.21, CI 0.90–1.63) and intracranial bleeding (RR 1.87, CI 0.94–3.70).
Conclusions Use of intermediate intensity warfarin with aspirin reduced the risk of stroke at the price of increased bleeding. Most anticoagulation increased the risk of major bleeding with no effect on mortality. Studies with oral anticoagulants with aspirin for secondary prevention should be considered.
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