Recurrent ischemic stroke in atrial fibrillation patients despite NOAC therapy: Recent advances and their therapeutic implications

Direct oral anticoagulants (DOACs) are currently the preferred anticoagulant therapy in patients with non-valvular atrial fibrillation. Nevertheless, for patients receiving oral anticoagulants, clinical trials reported a residual annual risk of recurrent ischemic events ranging from 0.7% to 2.3%, in both primary and secondary prevention settings. Furthermore, in the non-randomized RENO-EXTEND study, patients who had an ischemic stroke while on DOAC therapy, also had a recorded combined rate of thromboembolic and bleeding events of 16.7%, corresponding to the annual prevalence of 13.4%. Reliable evidence on how to proceed with management of those patients who experience ischemic stroke while receiving DOAC therapy, is limited. This patient setting needs to take into consideration the following strategies: 1) Exclude poor adherence to treatment; 2) Assess potential drug–drug interactions; 3) Ensure the prescription of the most appropriate DOAC dose; 4) Confirm the underlying mechanism of the recurrent ischemic event; 5) Continue with the same DOAC after a cardioembolic event occurring during DOAC therapy, when appropriate; 6) Consider switching to a different DOAC so to improve adherence; 7) Evaluate, on a case-by-case basis and for the shortest feasible duration, the possible addition of an antiplatelet agent to DOAC therapy; 8) Consider left atrial appendage occlusion combined with indefinite DOAC therapy in selected patients with recurrent events despite anticoagulation; 9) Implement stricter risk factor control. Moreover, results from randomized controlled trials investigating more effective management strategies are needed to improve treatment of patients in this setting.