Impact of bleeding events on mortality in patients with atrial fibrillation and silent left atrial thrombi: insight from the LAT trial

Abstract Background Thrombolytic therapy is important to prevent thromboembolism in patients with atrial fibrillation (AF) and left atrial (LA) thrombi. However, bleeding complications are a major concern. Purpose To investigate the incidence and prognosis of bleeding complications in patients with AF and silent LA thrombi. Methods An analysis was performed from the LAT trial, a multicenter observational study investigating outcomes of silent LA thrombi detected by trans-esophageal echocardiography (TEE) in AF patients. Of 17,436 patients who underwent TEE, 297 (median age, 70 years; 31% female, median CHA2DS2-VASc score of 4) were eligible for inclusion. Management of oral anticoagulants was at the physician’s discretion, and the follow-up period was set as 1-year. Major bleeding was defined as intracranial hemorrhage, bleeding requiring surgery or transfusion, or ≥4 g/dl decrease in hemoglobin level. Results Prescription rates of oral-anticoagulants at baseline and the final follow-up were 81.8% and 89.9%, respectively (p = 0.002). During a median follow-up of 385 (interquartile range, 365-411) days after the thrombi detection, the incidence of thromboembolism, major bleeding, and all-cause death was 5.7% (n = 17), 11.4% (n = 34) and 8.4 % (n = 25), respectively. Patients with thromboembolism were more likely experience subsequent death than those without thromboembolism (17.7% vs. 7.9%, log-rank p = 0.063). Similarly, patients with major bleeding more frequently experienced subsequent death than those without bleeding (20.6% vs. 6.8%, log-rank p = 0.002). Time-adjusted Cox regression analysis revealed a temporal association between major bleeding and subsequent death (hazard ratio, 3.72; 95% confidence interval 1.55–8.93; p = 0.003) as well as between thromboembolism and subsequent death (hazard ratio, 2.98; 95% confidence interval 0.89–9.99; p = 0.077). Conclusions In the LAT trial, about 10% of patients with AF and silent LA thrombi experienced major bleeding during 1-year follow-up. Not only thromboembolism but also major bleeding was strongly associated with subsequent death.