Rationale and design of the SAFE-A study: SAFety and Effectiveness trial of Apixaban use in association with dual antiplatelet therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.

BACKGROUND: Patients with atrial fibrillation who undergo coronary stenting require triple antithrombotic therapy, including aspirin, a P2Y12 inhibitor, and anticoagulation, to prevent both stroke and stent thrombosis. However, triple therapy may increase the risk of bleeding complications. The optimal management of triple therapy still presents a challenge in these patients.

HYPOTHESIS: We hypothesized that 1-month P2Y12 inhibitor treatment after drug-eluting stent (DES) implantation, as compared with 6-month P2Y12 inhibitor treatment, in combination with aspirin and apixaban, would be associated with a decrease in the incidence of bleeding complications in patients with atrial fibrillation who undergo DES implantation.

DESIGN: SAFE-A (UMIN Clinical Trials Registry Number: UMIN000015923) is a multicenter, prospective, randomized, open-label, blinded-endpoint, parallel-group, comparative study that was designed to compare the safety and efficacy of short-duration treatment with a P2Y12 inhibitor in combination with aspirin and apixaban in subjects with non-valvular atrial fibrillation who undergo DES implantation. A total of 600 subjects will be randomized in a 1:1 fashion to either 1-month or 6-month P2Y12 inhibitor therapy in combination with aspirin and apixaban. The primary endpoint is the incidence of all bleeding complications occurring within 12 months.

CONCLUSION: The SAFE-A study is the first randomized controlled trial to compare 1-month vs. 6-month P2Y12 inhibitor therapy in combination with aspirin and apixaban, in patients with atrial fibrillation who undergo DES implantation. This study will provide data that may guide the optimal management of triple antithrombotic therapy.