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

Non-vitamin K oral anticoagulants (NOACs) are currently the preferred anticoagulant therapy for patients with non-valvular atrial fibrillation. Nevertheless, for patients receiving oral anticoagulants, clinical trials have 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 NOAC therapy, also had a recorded combined rate of thromboembolic and bleeding events of 16.7%, corresponding to an annual incidence of 13.4%. For those patients who experience an ischemic stroke while receiving NOAC therapy, reliable evidence on how to proceed with management is limited. This patient setting need 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 NOAC dose; 4) Confirm the underlying mechanism of the recurrent ischemic event; 5) Continue the same NOAC after a cardioembolic event occurring during NOAC therapy, when appropriate; 6) Consider switching to a different NOAC 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 NOAC therapy; 8) Consider left atrial appendage occlusion combined with indefinite NOAC therapy in selected patients with recurrent events despite anticoagulation; 9) Increment stricter risk factor controls. Moreover, results from randomized controlled trials investigating for more effective management strategies are needed to better treat patients in this setting.