Stroke Prevention with Oral Anticoagulants: Summary of the Evidence and Efficacy Measures as an Aid to Treatment Choices

Atrial fibrillation (AF) is an established risk factor for a first or recurrent stroke. Despite proven efficacy in preventing stroke in patients with AF, warfarin is underused, partly due to safety concerns. Recent randomized trials have shown that non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran (a direct thrombin inhibitor) and apixaban, edoxaban, and rivaroxaban (factor Xa inhibitors) are not only non-inferior or superior to warfarin but also demonstrate a decreased risk of cerebrovascular bleeding among patients with AF and moderate to high risk of stroke. Additionally, NOACs have an advantage of requiring no monitoring of the international normalized ratio compared with warfarin. This review summarizes the published literature on NOACs for the primary and secondary prevention of ischemic strokes, with an emphasis on the expected absolute benefits from the introduction of such agents. As compared with warfarin, NOACs significantly reduce the risk of hemorrhagic stroke, and only dabigatran (150 mg twice daily) was found to significantly reduce the risk of ischemic stroke. However, measures of relative benefits from medical interventions do not immediately provide the estimated benefit to be derived from an individual patient, something best done by considering the expected absolute benefit. The number needed to treat (NNT) is presented for various outcomes in the phase 3 trials of NOACs. Despite the important progress achieved with the introduction of NOACs, the availability of at least four agents with different efficacy and safety performances in comparison with warfarin prompts the question of whether any of these agents is preferable to another. It is hoped that future studies on the efficacy, safety, and economic performance of NOACs will further allow for rational choices within this important therapeutic class. Meanwhile, the NNT may be a valid metric to be considered by clinicians faced with the need to make such choices.