Antithrombotic Therapy in Patients with Chronic Coronary Disease on Anticoagulation: Evidence from Contemporary Trials

INTRODUCTION: Chronic coronary disease (CCD) commonly coexists with long-term oral anticoagulation (OAC), particularly for atrial fibrillation (AF). Combination antiplatelet therapy increases bleeding, whereas ischemic protection with OAC alone remains a concern. We critically appraised contemporary evidence and guidelines to define optimal long-term maintenance therapy. METHODS: We synthesized WOEST, PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS, AFIRE, OAC-ALONE, PRAEDO-AF, EPIC-CAD, AQUATIC, and meta-analyses. Because foundational trials included recent ACS/PCI populations, evidence was analyzed as early/recent ACS or PCI (≤1 year) and late/stable CAD (>1 year post-PCI or non-revascularized CCD). Designs, populations, ischemic, bleeding, and mortality outcomes were systematically compared within the 2023 ACC/AHA CCD and AF guidelines. RESULTS AND DISCUSSION: Early trials supported aspirin withdrawal and DOAC plus single P2Y12 inhibition after PCI. Later trials showed full-dose OAC monotherapy was noninferior to OAC plus single antiplatelet therapy beyond 6-12 months or in stable non-revascularized CCD for preventing myocardial infarction, stroke, and systemic embolism, while reducing major and clinically relevant nonmajor bleeding and, sometimes, mortality. Meta-analysis showed fewer cardiovascular death, myocardial infarction, stroke, and major bleeding events without excess ischemia. CONCLUSION: OAC monotherapy should be the default for most patients, reserving antiplatelets for individualized high-ischemic/low-bleeding-risk scenarios, while recognizing predominantly East Asian and limited European evidence.