Statins, fenofibrate, and quinapril increase clot permeability and enhance fibrinolysis in patients with coronary artery disease

Abstract

Background: Aspirin increases fibrin clot porosity and susceptibility to lysis. It is unknownwhether other drugs, in combination with aspirin, used in the treatment of coronary artery disease (CAD) might affect clot structure and resistance to lysis. Aim: The aim of the study was to assess the effects of statins, fibrates, or angiotensin-converting enzyme inhibitors (ACEIs) on fibrin clot properties. Patients and methods: In a randomized double-blind study, men with advanced CAD taking low-dose aspirin were assigned to receive one of the four drugs: simvastatin 40 mg day-1 (n=13), atorvastatin 40 mg day-1 (n=12), fenofibrate 160 mg day)1 (n=12), and quinapril 10 mg day-1 (n=11) for 28 ± 2 days.Moreover, CAD patients (n=13) taking aspirin (75 mg day-1) for 8 weeks were studied after additional 4 weeks on an open-label basis. Thirty men served as healthy controls. Plasma clot permeability and tissue plasminogen activator-induced fibrinolysis were evaluated at baseline and after drug administration. Results: Permeability increased following the administration of simvastatin (by 20%; P=0.01), atorvastatin (by 22%; P=0.001), fenofibrate (by 16%; P=0.02), and quinapril (by 13%; P=0.04) like for aspirin (P < 0.001). Turbidity analysis showed that administration of any of the drugs was associated with higher maximum absorbancy, suggesting thicker fibers, and shorter fibrinolysis time (P < 0.001). Post-treatment reduction in lysis time correlated with an increase in clot porosity in all the groups (r from 0.42 to 0.61; P from 0.01 to 0.001). Conclusions: Statins, fibrates, and ACEIs may increase plasma clot permeability and susceptibility to fibrinolysis in CAD patients receiving aspirin. This novel antithrombotic mechanism might contribute to clinical benefits of the drugs tested.© 2006 International Society on Thrombosis and Haemostasis.