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American Journal of Medicine
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American Journal of Medicine
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There are of course therapies that represent alternatives to a vitamin K antagonist; however Figure 12 demonstrates that until recently those alternatives have not been anywhere near as effective as warfarin.[19] Warfarin clearly beats placebo or a low fixed-dose of warfarin, or antiplatelet therapy with aspirin or aspirin together with clopidogrel.[19] It was not until the direct thrombin inhibitor ximelagatran was investigated that warfarin's value in reducing stroke and systemic embolism was equaled. Ximelagatran was never approved because of hepatotoxicity, but several other new agents – called new or novel oral anticoagulants (NOACs) – have shown that they are either as effective as warfarin or superior to warfarin.[20] These include
• the direct thrombin inhibitor dabigatran, at two dose levels (110 or 150 mg);
• the first 2 approved factor Xa inhibitors, rivaroxaban and apixaban.
In addition to efficacy, these NOACs are also as good as or equal the effects of warfarin with regard to major bleeding. Importantly, all 3 of the NOACs shown here, including both doses of dabigatran are associated with significantly less intracranial hemorrhage than warfarin.[20] All of these results are derived from randomized trials of warfarin against these alternative therapies. Camm J. Am J Med 2013; published on-line at http://education.amjmed.com/00000.
[19] Lip GY, Edwards SJ. Stroke prevention with aspirin, warfarin and ximelagatran in patients with non-valvular atrial fibrillation: a systematic review and meta-analysis. Thromb Res. 2006;118:321-333.
[20] Dentali F, Riva N, Crowther M, et al. Efficacy and safety of the novel oral anticoagulants in atrial fibrillation: a systematic review and meta-analysis of the literature. Circulation. 2012;126:2381-2391.