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The presence of atrial fibrillation (AF), the most common sustained cardiac arrhythmia, significantly increases the risk for stroke. Current guidelines recommend that the vitamin K antagonist warfarin or direct oral anticoagulants (DOACs), such as the approved direct thrombin inhibitor dabigatran and the approved direct factor Xa inhibitors apixaban, rivaroxaban, and edoxaban, should be used for thromboprophylaxis in patients with nonvalvular AF at risk for stroke or systemic embolic events (SEE). Warfarin, the mainstay of stroke prevention in AF, increases the risk of major bleeding. Furthermore, warfarin therapy comes with several limitations including frequent monitoring and the need for dose adjustments, unpredictable pharmacokinetics and pharmacodynamics, and the potential for significant drug-drug and food-drug interactions. The DOACs were developed to overcome these limitations while maintaining or surpassing warfarin's efficacy and safety profiles. All four DOACs have similar or better efficacy and safety compared with warfarin and are therefore valuable alternatives for the prevention of stroke and SEE in patients with nonvalvular AF. Understanding the subtle differences in the DOACs' pharmacology, phase 3 study designs, and trial outcomes will allow for a more tailored approach in selecting the right oral anticoagulant for each patient.

Direct Oral Anticoagulants for the Prevention of Stroke in Patients with Nonvalvular Atrial Fibrillation: Understanding Differences and Similarities