Differential effect of statin use on coagulation markers: an active comparative analysis in the NEO study

Background: Statins are a potential treatment for venous thromboembolism (VTE) prophylaxis complementary to conventional anticoagulants without associated bleeding complications. The aim of this study was 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 procoagulant factor outcomes. Methods: This is a cross-sectional analysis of participants from the Netherlands Epidemiology of Obesity study who were using any class of lipid-lowering drugs, including any types of statins, niacin, and fibrates. We performed linear regression analyses to determine the activity of fibrinogen, factor (F)VIII, FIX, and FXI in statins versus fibrate/niacin users and adjusted for age, sex, tobacco smoking, body mass index (BMI), hypertension, diabetes, and prevalent cardiovascular disease. Results: Among 1043 participants, the mean age was 58.39± 5.19 years, 61% were men, and mean BMI was 31.3± 4.5 kg/m 2 . Clinical characteristics were balanced between statin and fibrate/niacin users. Statin users had lower mean FVIII (15.8 IU/dL, 95% confidence interval (CI) -0.003 to 31.6), FIX (11.3 IU/dL, 95% CI -0.4 to 23.2) and FXI (18.3 IU/dL, 95% CI 9.4 to 27.3) levels, and higher mean fibrinogen levels (19.1 mg/dL, 95% CI -10.0 to 48.2) compared to fibrate/niacin users. Conclusion: Current statin use was associated with lower plasma levels of FVIII, FIX, FXI, and higher fibrinogen levels compared to fibrate/niacin use. These effects on coagulation factors may, in part, explain the benefit of statin therapy rendered in primary and secondary prevention of VTE.