Rosuvastatin use reduces thrombin generation potential in patients with venous thromboembolism: a randomized controlled trial

Author(s)

Orsi, Fernanda A. ^{[1, 2]} ; Biedermann, Joseph S. ^{[3, 4]} ; Kruip, Marieke J. H. A. ^{[3, 4]} ; van der Meer, Felix J. ^[5] ; Rosendaal, Frits R. ^[2] ; Vlieg, Astrid van Hylckama ^[2] ; Bos, Mettine H. A. ^[6] ; Leebeek, Frank W. G. ^[3] ; Cannegieter, Suzanne C. ^{[2, 5]} ; Lijfering, Willem M. ^[2]

Affiliation

^[1] Univ Campinas Unicamp, Sch Med Sci, Dept Clin Pathol, Campinas, SP - Brazil

^[2] Leiden Univ, Med Ctr, Dept Clin Epidemiol, POB 9600, NL-2300 RC Leiden - Netherlands

^[3] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam - Netherlands

^[4] Erasmus Univ, Med Ctr, Star Med Anticoagulat Clin, Rotterdam - Netherlands

^[5] Leiden Univ, Med Ctr, Sect Thrombosis & Hemostasis, Dept Internal Med, Leiden - Netherlands

^[6] Leiden Univ, Med Ctr, Einthoven Lab Vasc & Regenerat Med Leiden, Leiden - Netherlands

• Document type: Journal article
• Source: Journal of Thrombosis and Haemostasis; v. 17, n. 2, p. 319-328, FEB 2019.
• Web of Science Citations: 1

Abstract

Background Statin therapy could form an alternative prophylactic treatment for venous thromboembolism (VTE) if statins are proven to downregulate hemostasis and prevent recurrent VTE, without increasing bleeding risk. Objectives The STAtins Reduce Thrombophilia (START) trial investigated whether statin affects coagulation in patients with prior VTE. Patients/methods After anticoagulation withdrawal, patients were randomized to rosuvastatin 20 mg day(-1) for 4 weeks or no intervention. Plasma samples taken at baseline and at the end of the study were analyzed employing thrombin generation assay. Results and conclusions The study comprised 126 rosuvastatin users and 119 non-users. Mean age was 58 years, 61% were men, 49% had unprovoked VTE and 75% had cardiovascular (CV) risk factors. Endogenous thrombin potential (ETP) increased from baseline to end of study in non-statin users (mean 97.22 nm{*}min; 95% CI, 40.92-153.53) and decreased in rosuvastatin users (mean -24.94 nm{*}min; 95% CI, -71.81 to 21.93). The mean difference in ETP change between treatments was -120.24 nm{*}min (95% CI, -192.97 to -47.51), yielding a 10.4% ETP reduction by rosuvastatin. The thrombin peak increased in both non-statin (mean 20.69 nm; 95% CI, 9.80-31.58) and rosuvastatin users (mean 8.41 nm; 95% CI -0.86 to 17.69). The mean difference in peak change between treatments was -11.88 nm (95% CI, -26.11 to 2.35), yielding a 5% peak reduction by rosuvastatin. Other thrombin generation parameters did not change substantially. The reduction in ETP and peak by rosuvastatin was more pronounced in the subgroups of participants with CV risk factors and with unprovoked VTE. We conclude that rosuvastatin reduces thrombin generation potential in patients who had VTE. (AU)

• FAPESP's process: 17/09506-5 - Identification of novel targets for therapy with PCSK9: From LDL lowering to decreased inflammation and coagulation
• Grantee: Fernanda Loureiro de Andrade Orsi
• Support Opportunities: Scholarships abroad - Research