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 compared to warfarin therapy. For older patients with atrial fibrillation (AF) and comorbidities, however, decisions on DOAC therapy may be challenging. In frail, stable-on-warfarin patients, the FRAIL-AF trial reported increased relevant bleeding with DOAC switching. However, subsequent individual patient-data analyses of the four pivotal DOAC-versus-warfarin AF trials confirmed 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 by renal function. All DOACs undergo variable renal clearance and, in Europe, a creatinine clearance <30mL/min contraindicates dabigatran and <15mL/min the factor-Xa inhibitors. AF patients on DOACs presenting with an acute coronary syndrome and/or requiring percutaneous coronary interventions are generally managed by 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 an 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 a non-severe hemorrhagic stroke during DOAC therapy, resuming a DOAC to prevent ischemic strokes is counterbalanced by considerably enhanced major bleeding, including intracranial.