Anticoagulant Regimen for Nonvalvular Atrial Fibrillation in the Elderly and Frail Population.

Anticoagulant therapy is the cornerstone of stroke prevention in atrial fibrillation (AF), yet its management in elderly and frail patients remains particularly challenging. This review aims to summarize current evidence, guideline recommendations, and future perspectives regarding the optimal anticoagulant strategy in this vulnerable population. A narrative review of pivotal randomized clinical trials and major real-world registries was conducted, focusing on outcomes of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients aged ≥75 years or meeting frailty criteria. Across studies, DOACs consistently demonstrated similar or superior efficacy compared with VKAs for the prevention of stroke and systemic embolism, with a substantially lower risk of intracranial hemorrhage. Apixaban and edoxaban, particularly at adjusted doses, showed the most favorable balance between thromboembolic protection and bleeding risk. Conversely, switching stable elderly patients from long-term VKAs to DOACs, as in the FRAIL-AF trial, was associated with an early excess of clinically relevant nonmajor bleeding. Frailty, multimorbidity, renal impairment, and polypharmacy remain critical modifiers of both efficacy and safety, underlining the need for individualized dosing and regular renal function monitoring. Recent European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) and the American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines recommend DOACs as the preferred treatment for nonvalvular AF, emphasizing comprehensive risk assessment and shared decision-making. Emerging agents, such as factor XI inhibitors, offer a promising approach to minimizing bleeding risk in the elderly, though confirmation of their efficacy against ischemic events remains to be fully established. In elderly and frail patients with AF, DOACs represent the first-line anticoagulant therapy when appropriately dosed and monitored. A personalized, multidisciplinary approach incorporating frailty assessment, renal evaluation, and patient preference is essential to optimize outcomes. Future trials specifically enrolling very old and severely frail patients are urgently needed to close existing evidence gaps.