Direct oral anticoagulants in older patients with atrial fibrillation and comorbidities: frailty, renal impairment, acute or chronic coronary syndromes, and acute stroke

Direct oral anticoagulants (DOACs) have been available since 2008, boosting appropriate anticoagulation and reducing intracranial hemorrhages, as compared with warfarin therapy. However, for older individuals with atrial fibrillation (AF) and comorbidities, decisions on DOAC therapy may be challenging. In frail, stable‑on‑warfarin patients, the FRAIL‑AF (Safety of Switching from a Vitamin K Antagonist to a Non-Vitamin K Antagonist Oral Anticoagulant in Frail Older Patients with Atrial Fibrillation) trial reported increased relevant bleeding after switching to a DOAC. Subsequent individual patient‑data analyses of 4 pivotal DOAC‑vs‑warfarin AF trials confirmed the overall advantages of DOACs over warfarin even among older, frail, warfarin‑experienced individuals. Advanced age should not exclude the use of any DOAC for AF, but care is needed to adjust the doses, when indicated, particularly based on renal function. All DOACs undergo variable renal clearance and, in Europe, creatinine clearance below 30 ml/min contraindicates dabigatran, and below 15 ml/min factor‑Xa inhibitors. AF patients on DOACs presenting with acute coronary syndrome and / or requiring percutaneous coronary interventions are generally managed with additional dual antiplatelet therapy for 1-4 weeks, followed by clopidogrel plus DOAC for up to 1 year. AF patients with chronic coronary syndromes should generally receive a DOAC without additional antiplatelet therapy, as this abates major bleeding and improves cardiovascular survival without evidence of increased ischemic risk. For AF patients who develop acute ischemic stroke, recent exposure to a DOAC is a relative contraindication to intravenous thrombolysis, but the latter may be considered when clinically‑relevant anticoagulation can be excluded. Finally, for AF patients who develop nonsevere hemorrhagic stroke during DOAC therapy, resuming a DOAC to prevent ischemic strokes is counterbalanced by considerably enhanced major bleeding, including intracranial.