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The Impact of Dabigatran and Rivaroxaban on Variation of Platelet Activation Biomarkers and DRT Following Percutaneous Left Atrial Appendage Closure

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. M...

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Autores principales: Li, Xiaoye, Zhang, Xiaochun, Jin, Qinchun, Li, Yanli, Zhou, Daxin, Lv, Qianzhou, Ge, Junbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479099/
https://www.ncbi.nlm.nih.gov/pubmed/34603033
http://dx.doi.org/10.3389/fphar.2021.723905
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author Li, Xiaoye
Zhang, Xiaochun
Jin, Qinchun
Li, Yanli
Zhou, Daxin
Lv, Qianzhou
Ge, Junbo
author_facet Li, Xiaoye
Zhang, Xiaochun
Jin, Qinchun
Li, Yanli
Zhou, Daxin
Lv, Qianzhou
Ge, Junbo
author_sort Li, Xiaoye
collection PubMed
description 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 CHA(2)DS(2)-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.
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spelling pubmed-84790992021-09-30 The Impact of Dabigatran and Rivaroxaban on Variation of Platelet Activation Biomarkers and DRT Following Percutaneous Left Atrial Appendage Closure Li, Xiaoye Zhang, Xiaochun Jin, Qinchun Li, Yanli Zhou, Daxin Lv, Qianzhou Ge, Junbo Front Pharmacol Pharmacology 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 CHA(2)DS(2)-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. Frontiers Media S.A. 2021-09-15 /pmc/articles/PMC8479099/ /pubmed/34603033 http://dx.doi.org/10.3389/fphar.2021.723905 Text en Copyright © 2021 Li, Zhang, Jin, Li, Zhou, Lv and Ge. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Li, Xiaoye
Zhang, Xiaochun
Jin, Qinchun
Li, Yanli
Zhou, Daxin
Lv, Qianzhou
Ge, Junbo
The Impact of Dabigatran and Rivaroxaban on Variation of Platelet Activation Biomarkers and DRT Following Percutaneous Left Atrial Appendage Closure
title The Impact of Dabigatran and Rivaroxaban on Variation of Platelet Activation Biomarkers and DRT Following Percutaneous Left Atrial Appendage Closure
title_full The Impact of Dabigatran and Rivaroxaban on Variation of Platelet Activation Biomarkers and DRT Following Percutaneous Left Atrial Appendage Closure
title_fullStr The Impact of Dabigatran and Rivaroxaban on Variation of Platelet Activation Biomarkers and DRT Following Percutaneous Left Atrial Appendage Closure
title_full_unstemmed The Impact of Dabigatran and Rivaroxaban on Variation of Platelet Activation Biomarkers and DRT Following Percutaneous Left Atrial Appendage Closure
title_short The Impact of Dabigatran and Rivaroxaban on Variation of Platelet Activation Biomarkers and DRT Following Percutaneous Left Atrial Appendage Closure
title_sort impact of dabigatran and rivaroxaban on variation of platelet activation biomarkers and drt following percutaneous left atrial appendage closure
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479099/
https://www.ncbi.nlm.nih.gov/pubmed/34603033
http://dx.doi.org/10.3389/fphar.2021.723905
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