Anticoagulation Drug Trials for Stroke Prevention in Atrial Fibrillation
Trials in the 1980s and 1990s showed that warfarin reduces stroke in patients with atrial fibrillation by approximately two-thirds, and that aspirin has either much less of an effect or no effect at all. The combination of aspirin and clopidogrel, compared with aspirin alone, reduces stroke by a relative 28% but has the same rate of major bleeding as that of warfarin, which is far more effective at preventing stroke. Four trials of non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin have shown similar or better prevention of stroke, about half the rate of intracranial hemorrhage, and a 10% relative reduction in all-cause mortality. AVERROES compared apixaban with aspirin and showed better prevention of stroke, with only modestly increased rate of major bleeding and similar rate of intracranial hemorrhage. Thus, the NOACs provide important advantages over warfarin, in addition to being more convenient without the need for anticoagulation monitoring and lacking many of the food and drug interactions seen with warfarin. Greater expense of the NOACs is a barrier for many patients. Patients with moderate or severe mitral stenosis and with severe renal impairment were excluded from the trials; thus warfarin remains the treatment of choice for these patients. Patients with mechanical prosthetic valves should be treated with warfarin since the one trial with NOACs showed that dabigatran was neither safe nor effective. A large number of trials have been conducted to study how to use NOACs for atrial fibrillation in a variety of clinical settings such as cardioversion, device placement, and coronary stenting
