Short-Term Anticoagulation versus Dual Antiplatelet Therapy for Preventing Device Thrombosis Following Left Atrial Appendage Closure: The ANDES Randomized Clinical Trial

Background: The optimal antithrombotic treatment following transcatheter left atrial appendage closure (LAAC) remains to be determined. The objective of this trial was to compare anticoagulation and antiplatelet therapy for preventing device-related thrombosis (DRT) following LAAC. Methods: Prospective multicenter international randomized trial comparing 2 different antithrombotic strategies for preventing DRT following LAAC in patients with non-valvular atrial fibrillation. Patients were randomized (1:1) to receive direct oral anticoagulants (DOAC) or dual antiplatelet therapy (DAPT, aspirin + clopidogrel) for 60 days. Patients had a transesophageal echocardiography (TEE) at 60 days, and the images were analyzed in a central echocardiography laboratory by experienced echocardiographers blinded to the allocated treatment. The primary outcome was DRT as determined by TEE at 60 days after LAAC in those patients receiving the allocated treatment at the time of TEE (per-protocol analysis). The safety outcome included all-cause mortality, stroke, bleeding, or DRT (site-reported and leading to a treatment change) within 60 days after LAAC in all randomized patients (intention-to-treat analysis). Results: A total of 510 patients (mean age 77±9 years, 35% of women) were included between October 2018 and May 2025, and 253 and 257 patients were randomized to the DOAC and DAPT groups, respectively. Of these, 399 patients underwent TEE and were receiving the allocated treatment at 60 days post-LAAC. The primary outcome occurred in 3 patients (1.5%) in the DOAC group compared to 8 patients (4.1%) in the DAPT group (difference, -2.7% [95%CI, -6.0% to 0.6% ], p=0.110). The safety outcome occurred in 52 patients (22.5%) in the DOAC group compared to 82 patients (34.9%) in the DAPT group (difference, -12.4% [95% CI: -20.6% to -4.2%], p=0.003), and differences were mainly driven by a lower rate of bleeding events in the DOAC group (44 patients [17.4%] vs 64 patients [24.9%], difference, -7.5% [95% CI, -14.6% to -0.4%], p=0.038). Conclusions: The use of DOAC after LAAC failed to reduce DRT compared to DAPT but it was associated with an improved safety profile. The results of this study should be interpreted with caution due to statistical power issues related the narrowed than expected between-group differences, and will need confirmation in future larger studies.