BACKGROUND: We evaluated the antithrombotic effects of statins and angiotensin-converting enzyme inhibitor (ACEI) drugs in patients with coronary artery disease (CAD). METHODS AND RESULTS:Blood coagulation at the site of microvascular injury was assessed in 26 males with CAD before and after treatment withquinapril (10 mg day-1; n=13) or atorvastatin (40 mg day-1; n=13) for 4 weeks and an additional 4 weeks of combined therapy (quinapril+atorvastatin). Rates of prothrombin and factor V activation (FVa), fibrinogen (Fbg) cleavage and FVa inactivation showed that both quinapril and atorvastatin decreased the rates of: formation of thrombin B-chain (by 30.6%, P=0.007; and by 34.3%, P=0.003), formation of thrombin-antithrombin complexes (by 30.4%, P=0.0002; and by 40%, P=0.001), FV activation (by 19.1%, P=0.03; and by 21.8%, P=0.005) and Fbg depletion (by 29.2%, P=0.004; and by 32.7%, P=0.001). Atorvastatin alone accelerated FVa inactivation (P=0.005). A further 4 weeks of combined therapy enhanced most anticoagulant effects only when atorvastatin was added to quinapril. CONCLUSIONS: In CAD patients, atorvastatin and quinapril slowed blood clotting at the site of microvascular injury after 28 days of therapy. Addition of atorvastatin to quinapril, but not quinapril to the statin, enhanced the anticoagulant effects. Our findings might help explain the reduced risk of myocardial infarction or stroke in patients treated with statins and/or ACEIs and the lack of clinical benefits from ACEI added to prior statin therapy in patients at cardiovascular risk.
RCT Entities:
BACKGROUND: We evaluated the antithrombotic effects of statins and angiotensin-converting enzyme inhibitor (ACEI) drugs in patients with coronary artery disease (CAD). METHODS AND RESULTS:Blood coagulation at the site of microvascular injury was assessed in 26 males with CAD before and after treatment with quinapril (10 mg day-1; n=13) or atorvastatin (40 mg day-1; n=13) for 4 weeks and an additional 4 weeks of combined therapy (quinapril+atorvastatin). Rates of prothrombin and factor V activation (FVa), fibrinogen (Fbg) cleavage and FVa inactivation showed that both quinapril and atorvastatin decreased the rates of: formation of thrombin B-chain (by 30.6%, P=0.007; and by 34.3%, P=0.003), formation of thrombin-antithrombin complexes (by 30.4%, P=0.0002; and by 40%, P=0.001), FV activation (by 19.1%, P=0.03; and by 21.8%, P=0.005) and Fbg depletion (by 29.2%, P=0.004; and by 32.7%, P=0.001). Atorvastatin alone accelerated FVa inactivation (P=0.005). A further 4 weeks of combined therapy enhanced most anticoagulant effects only when atorvastatin was added to quinapril. CONCLUSIONS: In CAD patients, atorvastatin and quinapril slowed blood clotting at the site of microvascular injury after 28 days of therapy. Addition of atorvastatin to quinapril, but not quinapril to the statin, enhanced the anticoagulant effects. Our findings might help explain the reduced risk of myocardial infarction or stroke in patients treated with statins and/or ACEIs and the lack of clinical benefits from ACEI added to prior statin therapy in patients at cardiovascular risk.