Apixaban enhances endogenous fibrinolysis in patients with atrial fibrillation

Spinthakis, Nikolaos, Gue, Ying ORCID: 0000-0001-9994-8915, Farag, Mohamed, Srinivasan, Manivannan, Wellsted, David, Arachchillage, Deepa RJ, Lip, Gregory YH ORCID: 0000-0002-7566-1626 and Gorog, Diana A (2019) Apixaban enhances endogenous fibrinolysis in patients with atrial fibrillation. EUROPACE, 21 (9). pp. 1297-1306.

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Official URL: http://dx.doi.org/10.1093/europace/euz176

Abstract

<h4>Aims</h4>Approximately 20% of ischaemic stroke patients exhibit spontaneous arterial recanalization, attributable to endogenous fibrinolysis, which strongly relates to improved functional outcome. The impact of oral anticoagulants on endogenous fibrinolysis is unknown. Our aim was to test the hypothesis that apixaban enhances endogenous fibrinolysis in non-valvular atrial fibrillation (NVAF).<h4>Methods and results</h4>In a prospective cross-sectional analysis, we compared endogenous fibrinolysis in NVAF patients (n = 180) taking aspirin, warfarin, or apixaban. In a prospective longitudinal study, patients were tested before and after apixaban (n = 80). Endogenous fibrinolysis was assessed using the Global Thrombosis Test (GTT) and thromboelastography (TEG). Endogenous fibrinolysis [measured by GTT lysis time (LT)] was shorter on apixaban compared with warfarin or aspirin [median 1850 (IQR 1591-2300) vs. 2758 (2014-3502) vs. 2135 (1752-2463) s, P < 0.0001]. Among TEG indices, a small but significant difference in clot lysis time (CLT) was observed [apixaban 60.0 (45.0-61.0) vs. warfarin 61.0 (57.0-62.0) vs. aspirin 61.0 (59.0-61.0) min, P = 0.036]. Apixaban improved endogenous fibrinolysis measured using the GTT [LT pre-treatment 2204 (1779-2738) vs. on-treatment 1882 (1607-2374) s, P = 0.0003], but not by using TEG. Change in LT (ΔLT) with apixaban correlated with baseline LT (r = 0.77, P < 0.0001). There was weak correlation between ΔLT and ΔCLT in response to apixaban (r = 0.28, P = 0.02) and between on-apixaban LT and CLT (r = 0.25, P = 0.022).<h4>Conclusion</h4>Apixaban enhances endogenous fibrinolysis, with maximal effect in those with impaired fibrinolysis pre-treatment. Apixaban-treated patients exhibit more favourable fibrinolysis profiles than those taking warfarin or aspirin. Whether apixaban may confer additional thrombotic risk reduction in NVAF patients with impaired fibrinolysis, compared to warfarin, merits further study.

Item Type:	Article
Uncontrolled Keywords:	Endogenous fibrinolysis, Thrombosis, Apixaban, Atrial fibrillation, Non-vitamin K antagonist oral anticoagulant
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	22 Jun 2021 09:49
Last Modified:	18 Jan 2023 22:33
DOI:	10.1093/europace/euz176
Open Access URL:	https://doi.org/10.1093/europace/euz176
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3127282