Rosuvastatin treatment decreases plasma procoagulant phospholipid activity after a VTE: A randomized controlled trial

Cathrine Ramberg, Kristian Hindberg, Joseph S Biedermann, Suzanne C Cannegieter, Felix J van der Meer, Omri Snir, Frank W G Leebeek, Marieke J H A Kruip, John-Bjarne Hansen, Willem M Lijfering, Cathrine Ramberg, Kristian Hindberg, Joseph S Biedermann, Suzanne C Cannegieter, Felix J van der Meer, Omri Snir, Frank W G Leebeek, Marieke J H A Kruip, John-Bjarne Hansen, Willem M Lijfering

Abstract

Background: Venous thromboembolism (VTE) is a frequent cardiovascular disease with severe complications, including recurrence and death. There is a great need for alternative prophylactic treatment options as anticoagulation is accompanied by increased bleeding risk. Statins are reported to reduce the risk of incident and recurrent VTE, but the mechanisms are elusive. Procoagulant phospholipids (PPL), and phosphatidylserine in particular, are crucial for efficient coagulation activation, but no studies have investigated the effect of statin treatment on plasma PPL activity.

Objectives: To investigate the impact of rosuvastatin treatment on plasma PPL activity and levels of extracellular vesicles (EVs).

Patients/methods: Patients with a history of VTE (≥18 years) allowed to stop anticoagulant treatment were randomized to either 20 mg/day of rosuvastatin treatment or no treatment for 28 days in the Statins Reduce Thrombophilia (NCT01613794) trial. Plasma samples were collected at baseline and study end. PPL activity was measured in samples from 245 participants using a factor Xa-dependent clotting assay and EV levels by flow cytometry.

Results: Rosuvastatin treatment yielded an overall 22% (95% confidence interval [CI] -38.2 to -5.8) reduction in PPL activity, and 37% (95% CI -62.9 to -11.2) reduction in PPL activity in participants with a history of pulmonary embolism. The effect of rosuvastatin on plasma PPL activity was not explained by changes in total cholesterol nor change in levels of total- or platelet-derived EVs.

Conclusions: Rosuvastatin treatment caused a substantial decrease in plasma PPL activity, suggesting that a PPL-dependent attenuation of coagulation activation may contribute to a reduced VTE risk following statin treatment.

Keywords: blood clotting; extracellular vesicles; phosphatidylserines; rosuvastatin; venous thromboembolism.

© 2021 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.

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