Effect of three-day atorvastatin administration on coagulation factors in patients with prior venous thromboembolism and healthy subjects. A preliminary study.

Abstract

Statins exert antithrombotic effects, which might contribute to reduced risk of venous thromboembolism (VTE). Rosuvastatin 20 mg/d administered for 4 weeks has been reported to decrease coagulation factors (F) VII, FVIII, and FXI in VTE patients. Moreover, in accordance with recent registry data in non-VTE subjects statins usage was associated with lower FXI. We investigated whether three doses of a statin decrease coagulation factors activity and if such changes can alter fibrin clot properties in VTE patients and healthy subjects. We enrolled 28 consecutive first-ever prior VTE patients after 6 months anticoagulation and 25 healthy controls well-matched for demographics and lipid profiles (aged 44 [IQR 34-51] years) in an interventional nonrandomized study. Before and after three doses of atorvastatin 40 mg/d, activity of FVII, FVIII, FIX, and FXI was measured, along with fibrin clot properties, including permeability (Ks) and clot lysis using 3 various assays. After 3-day statin administration we observed the decrease of FVII (by 6.2%, P= P=0.046) and FXI (by 8.6%, P=0.044), irrespectively of LDL-C reduction (by 24%, P<0.001), while other coagulation factors remained unaltered. Reduction of FVII and FXI activity was inversely correlated with Ks alterations (R=-0.292, P=0.034 and R=-0.335, P=0.014, respectively). After adjustment for age, studied group and fibrinogen level, the reduction of FXI was independently associated with an increase of fibrin clot permeability (B=-0.084, P=0.027). In conclusion, a three-day 40 mg atorvastatin administration is sufficient to reduce FVII and FXI activity in our pilot study, which is associated with favorable fibrin clot properties modification.