Abstract： Objective:To analyze the antithrombotic strategies in patients with atrial fibrillation (AF) combined with acute coronary syndrome (ACS), and their adverse cardiovascular events in real-world practice.Methods:This research was a single-center, prospective, observational study. The patients with AF combined with ACS from Chinese Academy of Medical Sciences Fuwai Hospital between 2017 and 2019 were selected, and were divided into anticoagulant therapy and non-anticoagulant therapy groups by physician′ experience and patients′ intention, and were also divided into 2017, 2018, and 2019 groups according to the time of consultation. One year follow-up was conducted for all patients, with the primary endpoint of cardiogenic stroke. The secondary study endpoint was defined as major adverse cardiovascular events (MACCE), including all-cause death, cardiogenic stroke, non-central nervous system embolism of the corpuscular circulation, myocardial infarction, target vessel revascularization, and ischemia-driven revascularization.Results:A total of 1?333 patients with AF combined with ACS were enrolled in this study. Nine hundred and twenty-two patients were male, the average age was 68.3±9.7. Among them, 534 patients received anticoagulation therapy, and 799 patients did not receive anticoagulation therapy. Compared with non-anticoagulant group, anticoagulant group had higher CHA 2DS 2-VASc score (3.7±1.9 vs. 4.3±1.8, P<0.001). Between 2017 and 2019, patients who received anticoagulation ( P<0.001, P for trend<0.001), dual antithrombotic therapy with oral anticoagulants (OAC) +single antiplatelet therapy (SAPT, P=0.018, P fort rend=0.006), and triple antithrombotic therapy with OAC+dual antiplatelet therapy (DAPT, P<0.001, P for trend<0.001) increased by years. In terms of primary endpoint, cardiogenic stroke occurred in 5 patients (0.6%, 5/799) in the non-anticoagulant group, and 19 patients (3.6%, 19/534) in the anticoagulant group. Log-rank test indicated that the difference was statistically significant ( P<0.001). Cardiogenic stroke occurred in 10 patients (2.3%, 10/429) in the 2017 group, 9 patients (1.6%, 9/573) in the 2018 group, and 5 patients (1.5%, 5/331) in the 2019 group. Log-rank test indicated that there was no statistical significance between the three groups ( P=0.604). In terms of secondary endpoints, 75 cases (9.4%, 75/799) of MACCE events occurred in the non-anticoagulant treatment group while 85 cases (15.9%, 85/534) occurred in the anticoagulant treatment group. Log-rank test indicated statistically significant differences ( P<0.001). There were 48 MACCE events in the 2017 group (11.2%, 48/429), 72 MACCE events in the 2018 group (12.6%, 72/573), and 40 MACCE events in the 2019 group (12.1%, 40/331). Log-rank test showed no statistical significance ( P=0.827) . Conclusion:In recent years, anticoagulation and combined antithrombotic therapy in patients with AF combined with ACS showed an increasing trend year by year, but the incidence of cardiogenic stroke and MACCE did not improve significantly, which may be related to the higher CHA 2DS 2-VASc score in the anticoagulation group. Future studies should focus on comprehensive managements in this special population, and adopt more active and reasonable anti-thrombotic strategies.