The role of triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention

Dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel forms the backbone of secondary prevention in patients with acute coronary syndromes (ACS) or who undergo percutaneous coronary intervention (PCI), but in patients with atrial fibrillation (AF), oral anticoagulation (OAC) is superior to antiplatelet therapy for the prevention of stroke and systemic embolism. Patients with AF who undergo PCI or have an ACS event therefore have an indication for both OAC and DAPT, so-called triple antithrombotic therapy. However, observational analyses have shown that the annual rate of major bleeding on triple therapy exceeds 10%. For this reason, five major randomized clinical trials have compared double antithrombotic therapy with OAC and a P2Y12 inhibitor versus triple therapy in patients with AF who underwent PCI or had an ACS event. Each of the trials showed that double antithrombotic therapy reduced the rate of major and clinically relevant non-major bleeding compared with triple therapy and was non-inferior for prevention of ischemic events, including cardiovascular death, myocardial infarction, or stroke. In the one trial that directly compared warfarin with a non-vitamin K antagonist oral anticoagulant (NOAC), apixaban reduced the rate of major or clinically relevant non-major bleeding compared with warfarin and was non-inferior with respect to prevention of ischemic events. As a result of these trials, consensus guidelines recommend that patients with AF who undergo PCI or have an ACS event should be treated with triple antithrombotic therapy (OAC + P2Y12 inhibitor + aspirin) for 7 days or less, followed by double antithrombotic therapy (OAC + P2Y12 inhibitor) for 6 to 12 months.