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]
Summary
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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