Anticoagulant Effects of Statins and Angiotensin-Converting Enzyme Inhibitors in Stable Patients with Coronary Artery Disease: Results of a Randomized Double Blind Study

Abstract number: P0564

Undas¹ A, Brummel² K, Potaczek¹ D, Stobierska-Dzierzek¹ B, Bryniarski¹ L, Szczeklik¹ A, Mann² K

¹¹Jagellonian University School of Medicine, Krakow, Poland ¹¹Jagellonian University School of Medicine, Krakow, Poland ²²University of Vermont, Burlington, VT, USA

Background:  Statins and angiotensin-converting enzyme inhibitors (ACEIs) decrease cardiovascular mortality and morbidity. Since major complications of coronary artery disease (CAD) are thrombotic by nature, it might be hypothesized that beneficial effects of statins and ACEIs involve inhibition of thrombus formation. Therefore, this randomized double-blind study was designed to evaluate antithrombotic effects of both drug classes in stable CAD patients.

Methods and results:  Tissue factor-initiated coagulation was assessed at the site of microvascular injury in 26 men with CAD randomly allocated for treatment with quinapril or atorvastatin for 4 weeks and with both drugs for additional 4 weeks. Time-courses of prothrombin activation, fibrinogen cleavage, and factor (F)V activation with FVa inactivation, determined by quantitative Western blotting, showed that both quinapril and atorvastatin decreased maximum rates of the formation of thrombin B-chain (by 30.6%, P= 0.007 and 34.3%, P= 0.003, respectively), thrombin-antithrombin complexes (by 30.4%, P= 0.0002 and 40%, P= 0.001, respectively), and activated FV generation (by 19.1%, P= 0.03 and 21.8%, P= 0.005, respectively). Only atorvastatin accelerated factor Va inactivation by 60 to 120 seconds (P= 0.005). Quinapril and atorvastatin reduced significantly the rate of fibrinogen depletion (by 29.2%, P= 0.004 and 32.7%, P= 0.001, respectively). Further 4 weeks of the combined therapy resulted in a significant enhancement of the anticoagulant effects observed with the first 4 weeks only when atorvastatin was added to quinapril.

Conclusions:  Our results indicate that statins and ACEIs may produce similar anticoagulant actions in vivo within the first month of therapy in CAD patients, and addition of atorvastatin to quinapril for additional 28 days augmented the inhibition of coagulation.