A Clinically Oriented Review of the Landmark Clinical Trials Comparing Warfarin and Aspirin to Novel Oral Anticoagulants in Atrial Fibrillation

Objective: Until recently, oral anticoagulant drug options for patients with atrial fibrillation were limited to vitamin K antagonists. Over the last few years, three novel oral anticoagulants have been approved by the FDA for prevention of stroke and systemic embolism in atrial fibrillation and a fourth drug is currently under consideration for FDA approval. Recent large clinical trials have compared these four novel oral anticoagulants to warfarin or aspirin and found them to be non-inferior or superior for the prevention of stroke and systemic embolism in atrial fibrillation without increasing the risk of major bleeding. Furthermore, all four novel oral anticoagulants have been shown to significantly decrease the risk of intracranial hemorrhage compared to warfarin. Understanding the similarities and differences among these new anticoagulant drugs is of paramount importance when choosing the optimal anticoagulant for an individual patient. Detailed evaluation and understanding of the subtle nuances in clinical outcomes between the various anticoagulants in different trials allows the practicing clinician to make a better informed decision when recommending oral anticoagulation to patients. This review provides a clinically relevant discussion of the landmark novel oral anticoagulant trials in atrial fibrillation and provides specific recommendations to inform the practicing clinician.