Alternatives to chronic warfarin therapy for the prevention of stroke in patients with atrial fibrillation

Atrial fibrillation (AF) is associated with a fivefold increased risk for stroke due to thromboembolic events. Warfarin remains the standard medical therapy for decades in these patients but is difficult to use safely and conveniently. Chronic warfarin therapy is contraindicated in 14% to 44% of patients with AF who are at risk for stroke. In clinical practice, warfarin is prescribed to only 15% to 60% of patients with AF who are at high risk for thromboembolic events and have no clear contraindication to their use. Alternatives to warfarin include (i) antiplatelet therapy; (ii) new oral anticoagulants; and (iii) exclusion of the left atrial appendage (LAA) as a major embolic source. Dual antiplatelet therapy with aspirin and clopidogrel was superior to aspirin alone in reducing the risk of stroke in patients unsuitable to warfarin. Furthermore, a number of newer oral anticoagulants are currently under investigation for stroke prevention in AF. Oral direct thrombin or factor Xa inhibitors are in the most advanced stages of development. Given that about 90% of the source of thromboembolism occurs in the LAA in patients with non-valvular AF, occlusion of flow into the LAA may prevent thrombus formation in the appendage and hence reduction of stroke. Recently, several devices have been employed percutaneously with encouraging results in selected patients. Current review summarizes the latest clinical trial data pertinent to dual-antiplatelet therapy, several newer antithrombotic agents and LAA occlusion.