Abstract

BackgroundStatins are a potential treatment for venous thromboembolism (VTE) prophylaxis complementary to conventional anticoagulants without associated bleeding complications. This study aimed to compare pro-thrombotic activities of different classes of lipid-lowering drugs in an active comparator design and determine whether there is a relation between statin versus fibrate/niacin use and pro-coagulant factor outcomes.MethodsThis is a cross-sectional analysis of participants from the Netherlands Epidemiology of Obesity study using any class of lipid-lowering drugs, including any types of statins, niacin, and fibrates. We performed linear regression analyses to determine fibrinogen, factor (F) VIII, FIX, and FXI activity in statins versus fibrate/niacin users and adjusted for age, sex, tobacco smoking, body mass index (BMI), hypertension, diabetes, and prevalent cardiovascular disease.ResultsAmong 1043 participants, the mean age was 58.4 ± 5.2 years, 61% were men, and the mean BMI was 31.3 ± 4.5 kg/m2. Clinical characteristics were balanced between statin and fibrate/niacin users. Statin users had lower mean FXI (18.3 IU/dL, 95% confidence interval (CI) 9.4 to 27.3) levels compared to fibrate/niacin users. The level of FVIII (15.8 IU/dL, 95% CI − 0.003 to 31.6), and FIX (11.3 IU/dL, 95% CI − 0.4 to 23.2) were lower in statin users than fibrate/niacin users with marginal statistical significance.ConclusionCurrent statin use was associated with lower plasma levels of FXI than fibrate/niacin use. The effects on coagulation factors may, in part, explain the benefit of statin therapy rendered in primary and secondary prevention of VTE.

Highlights

  • Venous thromboembolism (VTE) has an estimated annual incidence rate of 1–2 per 1000 person-years among people of European ancestry [1]

  • Bordbar et al Thrombosis Journal (2021) 19:45 effects on the vessel wall and anti-thrombotic properties [12, 13]. These include decreased tissue factor expression and thrombin generation, impairment of procoagulant reactions catalyzed by thrombin including fibrinogen cleavage and factor (F) V and FXIII activation, reduction of FVII and FVIII activity, enhanced endothelial thrombomodulin expression, and upregulation of fibrinolytic activity manifested by decreased plasminogen activator inhibitor (PAI)-1 and increased tissue plasminogen activator expression [14, 15]

  • We aimed to examine whether there is a relation between statin use and pro-coagulant factor outcomes in individuals participating in the Netherlands Epidemiology of Obesity (NEO) study [21]

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Summary

Introduction

Venous thromboembolism (VTE) has an estimated annual incidence rate of 1–2 per 1000 person-years among people of European ancestry [1]. Statins have anti-inflammatory and anti-oxidant properties besides their lipid-lowering effects [10, 11] It has been postulated by mainly in-vitro studies and observational studies that they may have beneficial. Bordbar et al Thrombosis Journal (2021) 19:45 effects on the vessel wall and anti-thrombotic properties [12, 13] These include decreased tissue factor expression and thrombin generation, impairment of procoagulant reactions catalyzed by thrombin including fibrinogen cleavage and factor (F) V and FXIII activation, reduction of FVII and FVIII activity, enhanced endothelial thrombomodulin expression, and upregulation of fibrinolytic activity manifested by decreased plasminogen activator inhibitor (PAI)-1 and increased tissue plasminogen activator (tPA) expression [14, 15]. Statins are a potential treatment for venous thromboembolism (VTE) prophylaxis complementary to conventional anticoagulants without associated bleeding complications. This study aimed to compare prothrombotic activities of different classes of lipid-lowering drugs in an active comparator design and determine whether there is a relation between statin versus fibrate/niacin use and pro-coagulant factor outcomes

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