Role of Emerging Antithrombotic Therapy in the Prevention of Cardioembolic Complications in Patients with Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is an independent risk factor of potentially catastrophic cardioembolic strokes. AF patients are categorized into high-, intermediate-, and low-risk for thromboembolic complications using the CHADS2 or CHA2DS2-VASc scoring system. Oral anticoagulation using warfarin has been the standard therapy for stroke prevention in intermediate- to high-risk AF patients. However, warfarin use has been limited by several factors such as narrow therapeutic windows, drug-drug and drug-food interactions, and hemorrhagic complications. Rigorous research evaluated dual antiplatelet therapy of clopidogrel and aspirin (acetylsalicylic acid) as a potential alternative to warfarin in the ACTIVE W trial. Dual antiplatelet therapy of clopidogrel and aspirin was found to be inferior to warfarin in preventing stroke and systemic embolism with increased bleeding risk. Other extensive research has led to the development of new antithrombotic agents. Recently, dabigatran etexilate 150 mg twice daily, a direct thrombin inhibitor, was approved by the US FDA for stroke prevention in patients with non-valvular AF after it was found to be superior to warfarin in preventing thromboembolic events and associated with less bleeding in the RE-LY trial. It was also cost effective when compared with warfarin. Dabigatran can be considered in high-risk AF patients who are unable or unwilling to comply with the frequent laboratory and clinic visits that are required when receiving treatment with warfarin. Factor Xa inhibitors are another class of new anticoagulants that have been developed. Oral rivaroxaban was non-inferior to warfarin in thromboprophylaxis and with similar bleeding in the ROCKET-AF trial (HR 0.88; p=0.117). Apixaban, another factor Xa inhibitor, was superior to aspirin in reducing stroke and systemic embolism in patients with AF in the AVERROES trial (HR 0.45; p<0.001). The results of the ARISTOTLE trial, which is evaluating apixaban against warfarin in ∼18 000 patients with AF, are expected to be available later this year. Edoxaban, another oral factor Xa inhibitor, is currently being evaluated against warfarin in the ENGAGE AF-TIMI 48 trial in ∼20 000 patients with AF. With these new developments, there is a necessity for the clinical practitioner to become familiar with these new and upcoming therapies and guidelines. This review provides an overview of the available data regarding the clinical usefulness of these agents.