Antithrombotic Therapy in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

Antithrombotic therapy management in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remains challenging as it requires simultaneous protection from cardioembolism and coronary ischemic events while minimizing bleeding. The coexistence of these competing risks, along with their different temporal profiles, has driven a major shift in therapeutic strategies over the past decade. Randomized trials have consistently shown that direct oral anticoagulant (DOAC)-based dual antithrombotic therapy (DAT) reduces bleeding as compared with prolonged triple antithrombotic therapy (TAT), supporting early aspirin withdrawal in most patients. At the same time, pooled analyses suggest that this simplification may be accompanied by a small increase in ischemic risk, particularly during the first month after PCI, when the hazard of stent thrombosis is the highest. Contemporary guideline recommendations from Europe and North America are now broadly aligned in favoring a short periprocedural course of TAT followed by DAT with a DOAC and clopidogrel, then transitioning to oral anticoagulant monotherapy. However, important uncertainty remains for patients with very high ischemic or bleeding risk, including those with acute coronary syndromes, complex PCI, prior stent thrombosis, frailty, chronic kidney disease, previous bleeding, or active cancer. In these settings, treatment decisions cannot rely solely on trial-derived estimates or isolated risk scores, but require individualized, dynamic, and phase-specific assessments. This review critically appraises the biologic rationale, randomized evidence, and contemporary guideline recommendations for antithrombotic therapy in patients with AF undergoing PCI, focusing on areas not fully resolved by current guidelines, including modulation strategies, high-risk and underrepresented populations, tailored antithrombotic management, and emerging therapeutic directions.