Left atrial appendage closure is an alternative to chronic oral anticoagulation to prevent embolic events related to nonvalvular atrial fibrillation. After device implantation, antithrombotic treatment is prescribed to prevent device-related thrombosis, a dreadful complication associated with an increased risk of ischemic events. However, the optimal antithrombotic treatment after left atrial appendage closure, effective on both device-related thrombus prevention and bleeding risk mitigation, remains to be determined. In more than 10 years experience with left atrial appendage closure, a wide range of antithrombotic treatments have been used, mostly in observational studies. In this review, we analyzed the body of evidence for each antithrombotic regimen after left atrial appendage closure to provide tools to guide the physician choice and describe future perspectives in the field.

BACKGROUND: The optimal antithrombotic treatment after 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) after LAAC. METHODS: This was a prospective multicenter international randomized trial comparing 2 different antithrombotic strategies for preventing DRT after LAAC in patients with nonvalvular atrial fibrillation. Patients were randomized (1:1) to receive direct oral anticoagulants (DOACs) or dual antiplatelet therapy (DAPT; aspirin+clopidogrel) for 60 days. Patients underwent transesophageal echocardiography 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 transesophageal echocardiography 60 days after LAAC in patients receiving the allocated treatment at the time of transesophageal echocardiography (per-protocol analysis). The safety outcome included all-cause mortality, stroke, bleeding, or site-reported DRT 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% 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 transesophageal echocardiography and were receiving the allocated treatment at 60 days after LAAC. The primary outcome occurred in 3 patients (1.5%) in the DOAC group compared with 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 with 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%] versus 64 patients [24.9%]; difference, −7.5% [95% CI, −14.6% to −0.4%]; P =0.038). CONCLUSIONS: The use of DOACs after LAAC failed to reduce DRT compared with DAPT, but it was associated with an improved safety profile. The results of this study should be interpreted with caution because of statistical power issues related to the narrower-than-expected between-group differences and will need confirmation in future larger studies. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03568890.

The optimal antithrombotic strategy following left atrial appendage occlusion (LAAO) is not yet clearly established. Low-dose non-vitamin K antagonist oral anticoagulants (NOAC) might represent a valid alternative, but data regarding their usage is scarce. The aim of this study was to examine the efficacy and safety of low-dose NOAC compared to single (SAPT) or dual antiplatelet therapies (DAPT) after LAAO. We included consecutive patients with non-valvular atrial fibrillation who underwent LAAO and received low-dose apixaban, SAPT, or DAPT at discharge. The primary objective of this study included an efficacy endpoint (thromboembolic events and device related thrombosis (DRT)) and a safety endpoint (incidence of major bleeding) within the first three months after LAAO. A total of 139 patients were included. This group involved SAPT in 26 (18%), DAPT in 73 (53%), and apixaban in 40 (29%) patients. Follow-up at three-months showed no significant differences in the primary efficacy endpoint (2 (8%) SAPT, 3 (4%) DAPT and 0 (0%) apixaban; p value = 0.25). In contrast, the primary safety endpoint occurred more frequently in DAPT patients (7 (10%) DAPT, 0 (0%), SAPT and 0 with apixaban; p value = 0.03). Combining both efficacy and safety outcomes, low dose apixaban had a lower rate of events (2 (8%) with SAPT, 9 (12%) with DAPT and 0 (0%) with apixaban; p = 0.046). Low-dose apixaban after LAAO may be a valid alternative to DAPT and SAPT as depicted by the reduction in the occurrence of major bleedings and combined DRT/major bleedings respectively. Randomized data will be necessary to validate this strategy.