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

Direct oral anticoagulants (DOACs) are currently the preferred anticoagulant therapy in patientswith non-valvular atrial fibrillation. Nevertheless, for patients receiving oral anticoagulants, clinicaltrials reported a residual annual risk of recurrent ischemic events ranging from 0.7% to 2.3%, in bothprimary and secondary prevention settings. Furthermore, in the non-randomized RENO-EXTENDstudy, patients who had an ischemic stroke while on DOAC therapy, also had a recorded combinedrate of thromboembolic and bleeding events of 16.7%, corresponding to the annual prevalence of13.4%. Reliable evidence on how to proceed with management of those patients who experienceischemic stroke while receiving DOAC therapy, is limited. This patient setting needs to take intoconsideration the following strategies: 1) Exclude poor adherence to treatment; 2) Assess potentialdrug-drug interactions; 3) Ensure the prescription of the most appropriate DOAC dose; 4) Confirmthe underlying mechanism of the recurrent ischemic event; 5) Continue with the same DOAC aftera cardioembolic event occurring during DOAC therapy, when appropriate; 6) Consider switching toa 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 leftatrial appendage occlusion combined with indefinite DOAC therapy in selected patients with recurrentevents 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.