Stroke prevention with aspirin, warfarin and ximelagatran in patients with non-valvular atrial fibrillation: a systematic review and meta-analysis.
OBJECTIVE
To compare the effectiveness of aspirin, warfarin, and ximelagatran as thromboprophylaxis in patients with non-valvular atrial fibrillation (NVAF).


METHODS
Systematic review of randomised controlled trials in patients with NVAF treated with adjusted-dose warfarin and aspirin, fixed low-dose (FLD) warfarin, ximelagatran or placebo. Outcome measures studied were ischaemic stroke, systemic embolism, mortality and haemorrhage. Meta-analysis was performed using a fixed effects model.


RESULTS
We identified 13 trials (n=14,423 participants) of sufficient quality to be included in the analysis. Adjusted-dose warfarin significantly reduced the risk of ischaemic stroke or systemic embolism compared with aspirin (relative risk [RR] 0.59; 95% confidence interval [CI]: 0.40 to 0.86), FLD warfarin (RR 0.36; 95% CI: 0.23 to 0.58), or placebo (RR 0.33; 95% CI: 0.24 to 0.45). However, aspirin and placebo had a lower risk of major bleeding compared to warfarin (RR 0.58; 95% CI: 0.35 to 0.97 and RR 0.45; 95% CI: 0.25 to 0.82, respectively). The oral direct thrombin inhibitor, ximelagatran was as effective as adjusted-dose warfarin in the prevention of ischaemic strokes or systemic emboli (RR 1.04; 95% CI: 0.77 to 1.40) with less risk of major bleeding (RR 0.74; 95% CI: 0.56 to 0.96). Adjusted-dose warfarin significantly reduced mortality compared to placebo (RR 0.69; 95% CI: 0.53 to 0.89), but not for any of the other comparisons (aspirin: RR 0.87; 95% CI: 0.67 to 1.13; FLD warfarin: RR 1.11; 95% CI: 0.81 to 1.52; ximelagatran: RR 1.04; 95% CI: 0.86 to 1.26).


CONCLUSIONS
We have extended previous analyses, making this the largest systematic review and meta-analysis of thromboprophylaxis trial data in AF--and have included recent trials with the new oral direct thrombin inhibitor, ximelagatran. This systematic review confirms the superiority of anticoagulation therapy over aspirin as thromboprophylaxis in patients with NVAF. The new oral direct thrombin inhibitor, ximelagatran, appears as effective as adjusted-dose warfarin for the prevention of thromboembolic events in NVAF, with a lower risk of bleeding.
Lip
Gregory Y H
GY
Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK. g.y.h.lip@bham.ac.uk
Edwards
Steven J
SJ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D000925:Anticoagulants / Q000008:administration & dosage; D001241:Aspirin / Q000008:administration & dosage*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000453:epidemiology*; D001384:Azetidines / Q000008:administration & dosage*; D001596:Benzylamines / Q000008:administration & dosage*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D015897:Comorbidity; D004338:Drug Combinations; D006801:Humans; D020521:Stroke / Q000453:epidemiology* / Q000517:prevention & control*; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; D004338:Drug Combinations; C426686:ximelagatran; D014859:Warfarin; D001241:Aspirin