Apixaban enhances endogenous fibrinolysis in patients with atrial fibrillation.

Nikolaos Spinthakis, Ying Gue, Mohamed Farag, Manivannan Srinivasan, David Wellsted, Deepa R J Arachchillage, Gregory Y H Lip, Diana A Gorog

Journal: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2020;21(9):1297-1306

PMID: 31505618

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Abstract

AIMS

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).

METHODS AND RESULTS

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).

CONCLUSION

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.

Address: School of Life and Medical Sciences, Postgraduate Medical School, University of Hertfordshire, Hertfordshire, UK.; Department of Cardiology, East and North Hertfordshire NHS Trust, Hertfordshire, UK.; Department of Haematology, Royal Brompton Hospital, London, UK.; Department of Haematology, Imperial College Healthcare NHS Trust, London, UK.; Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool Heart & Chest Hospital, Liverpool, UK.; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.; Faculty of Medicine, National Heart & Lung Institute, Imperial College, Dovehouse Street, London, London, UK.

DOI: 10.1093/europace/euz176

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MeSH Terms: Aged, Aged, 80 and over, Anticoagulants, Aspirin, Atrial Fibrillation, Blood Coagulation Tests, Cross-Sectional Studies, Factor Xa Inhibitors, Female, Fibrin Clot Lysis Time, Fibrinolysis, Humans, Ischemic Stroke, Longitudinal Studies, Male, Middle Aged, Platelet Aggregation Inhibitors, Prospective Studies, Pyrazoles, Pyridones, Thrombelastography, Warfarin