Abstract

Background: The current post-procedure antithrombotic recommendation for left atrial appendage closure (LAAC) remains empiric. This study was designed to compare variations in platelet activation biomarkers and device-related thrombosis (DRT) under different antithrombotic regimens following LAAC.Methods: This study enrolled 105 consecutive patients with atrial fibrillation who underwent LAAC successfully and received post-procedure anticoagulation with either dabigatran (N = 33) or rivaroxaban (N = 72). After 3 months of anticoagulation treatment, thromboelastogram was used to evaluate thrombin receptor–activating peptide (TRAP)–induced platelet aggregation (PA). Measurements of platelet activation biomarkers, including thrombin–antithrombin complex (TAT), P-selectin, von Willebrand disease (vWF), and CD40L, were performed immediately before the LAAC procedure and after 3 months of post-procedure anticoagulation. Repeated transesophageal echocardiography was performed to evaluate DRT during follow-ups.Results: Three (4.2%) patients in the rivaroxaban and 4 (12.1%) patients in the dabigatran group experienced DRT events (odds ratio (OR) = 0.315, 95% confidence interval (95%CI): 0.066–1.489, p = 0.129) during follow-ups. The TRAP-induced PA was statistically significantly higher in the dabigatran group (62.9% vs 59.7%, p = 0.028*). Statistically significant increases in plasma concentration of TAT, P-selectin, and vWF were observed after 3 months of exposure to dabigatran when compared with rivaroxaban. An increased expression of platelet activation biomarkers was observed in DRT subjects compared with non–DRT subjects in terms of P-selectin and vWF (65.28 ± 13.93 ng/L vs 32.14 ± 12.11 ng/L, p = 0.037; 501.92 ± 106.48 U/L vs 280.98 ± 54.10 U/L, p = 0.045; respectively). Multivariate regression analysis indicated that the use of dabigatran might be an independent predictor of DRT (p = 0.022; OR = 4.366, 95%CI: 0.434–10.839). Furthermore, the CHA2DS2-VASc score (OR = 2.076, p = 0.016) and CD40L levels (OR = 1.015, p = 0.021) were independent predictors of increased D-dimer levels.Conclusions: Post-LAAC anticoagulation with dabigatran may increase the risk of DRT by enhancing platelet reactivity. In light of this potential increased risk in DRT, the authors recommend against using dabigatran for post-procedural anticoagulation in patients who have undergone LAAC.

Highlights

  • Percutaneous left atrial appendage closure (LAAC) has become an effective and safe surgical method for the prevention of stroke

  • The major findings of this study are as follows: 1) platelet activation biomarkers (TAT, P-selectin, and vWF) tended to increase, and platelet aggregation (PA) was activated by dabigatran; 2) dabigatran was associated with higher device-related thrombosis (DRT) rate mediated by increasing P-selectin and vWF levels; 3) CHA2DS2-VASc thrombosis score and CD40L levels may be important predictors of thrombosis after 3-month anticoagulation following LAAC

  • Rivaroxaban has been shown to be superior in preventing periprocedural DRT; it is suggested that uninterrupted rivaroxaban should be used as the choice of anticoagulant in patients undergoing occluder implantations or LAAC

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Summary

Introduction

Percutaneous left atrial appendage closure (LAAC) has become an effective and safe surgical method for the prevention of stroke. It is mainly available for patients who are diagnosed with non–valvular atrial fibrillation (NVAF) and who cannot adhere to long-term anticoagulant therapy (Iskandar et al, 2016; Reddy et al, 2017; Reddy, 2018). Current guidelines recommend that patients could be on direct oral anticoagulation (DOAC) after LAAC operation for 3 months to prevent DRT, dual antiplatelet therapy should be continued for up to 6 months, followed by taking aspirin lifelong when DRT is excluded (Glikson et al, 2019). This study was designed to compare variations in platelet activation biomarkers and device-related thrombosis (DRT) under different antithrombotic regimens following LAAC

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