Antiatherothrombotic Properties of Statins (original) (raw)
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The evolving role of statins in the management of atherosclerosis
Journal of the American College of Cardiology, 2000
Significant advances in the management of cardiovascular disease have been made possible by the development of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors-"statins." Initial studies explored the impact of statin therapy on coronary artery disease (CAD) progression and regression. Although the angiographic changes were small, associated clinical responses appeared significant. Subsequent large prospective placebocontrolled clinical trials with statins demonstrated benefit in the secondary and primary prevention of CAD in subjects with elevated cholesterol levels. More recently, the efficacy of statins has been extended to the primary prevention of CAD in subjects with average cholesterol levels. Recent studies also suggest that statins have benefits beyond the coronary vascular bed and are capable of reducing ischemic stroke risk by approximately one-third in patients with evidence of vascular disease. In addition to lowering low-density lipoprotein (LDL) cholesterol, statin therapy appears to exhibit pleiotropic effects on many components of atherosclerosis including plaque thrombogenicity, cellular migration, endothelial function and thrombotic tendency. Growing clinical and experimental evidence indicates that the beneficial actions of statins occur rapidly and yield potentially clinically important antiischemic effects as early as one month after commencement of therapy. Future investigations are warranted to determine threshold LDL values in primary prevention studies, and to elucidate effects of statins other than LDL lowering. Finally, given the rapid and protean effects of statins on determinants of platelet reactivity, coagulation, and endothelial function, further research may establish a role for statin therapy in acute coronary syndromes.
The lipid and non-lipid effects of statins
Pharmacology & Therapeutics, 2003
The 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors, more commonly known as statins, are a class of drug widely used for the treatment of hypercholesterolaemia in patients with established cardiovascular disease as well as those at high risk of developing atherosclerosis. Their predominant action is to reduce circulating levels of low-density lipoprotein (LDL) cholesterol; to a smaller degree, they also increase high-density lipoprotein (HDL) cholesterol and reduce triglyceride concentrations. In recent years, however, there has been an increasing body of evidence that their effects on lipid profile cannot fully account for their cardiovascular protective actions: their beneficial effects are too rapid to be easily explained by their relatively slow effects on atherogenesis and too large to be accounted for by their relatively small effects on plaque regression. Experimental models have revealed that statins exert a variety of other cardiovascular effects, which would be predicted to be of clinical benefit: they possess anti-inflammatory properties, as evidenced by their ability to reduce the accumulation of inflammatory cells in atherosclerotic plaques; they inhibit vascular smooth muscle cell proliferation, a key event in atherogenesis; they inhibit platelet function, thereby limiting both atherosclerosis and superadded thrombosis; and they improve vascular endothelial function, largely through augmentation of nitric oxide (NO) generation. The relative importance of the lipid-and non-lipid-related effects of the statins in the clinical situation remains the subject of much continuing research.
Cardiovascular effects of statins, beyond lipid-lowering properties
Pharmacological Research, 2014
The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, better known as 'statins', are amongst the most widely used medications in the world. They have become a pivotal component in the primary and secondary prevention of coronary artery and vascular disease. However, a growing amount of evidence has suggested that statins also possess strong pleiotropic effects irrespective of their lipid-lowering properties, which include enhancement of endothelial function, anti-inflammatory and anti-atherothrombotic properties, and immunomodulation. The following provides a comprehensive and updated review of the clinical evidence regarding the pleiotropic effects of statins in cardiovascular disorders and their potential therapeutic benefits.
Vascular and endovascular surgery, 2010
3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA-reductase) inhibitors, otherwise known as statins, are currently the medical treatment of choice for hypercholesterolemia. Hypercholesterolemia is a known risk factor for cardiovascular disease, and statin therapy has led to a significant reduction in morbidity and mortality from adverse cardiac events, stroke, and peripheral arterial disease. In addition to achieving a therapeutic decrease in serum cholesterol levels, statin therapy appears to promote other effects that are independent of changes in serum cholesterol. These ''pleiotropic'' effects include attenuation of vascular inflammation, improved endothelial cell function, stabilization of atherosclerotic plaque, decreased vascular smooth muscle cell migration and proliferation, and inhibition of platelet aggregation. This article is part I of a 2-part review, and it focuses on the pleiotropic effects of statins at the cellular level.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2004
The 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors (statins) have been shown to exhibit several vascular protective effects, including antithrombotic properties, that are not related to changes in lipid profile. There is growing evidence that treatment with statins can lead to a significant downregulation of the blood coagulation cascade, most probably as a result of decreased tissue factor expression, which leads to reduced thrombin generation. Accordingly, statin use has been associated with impairment of several coagulant reactions catalyzed by this enzyme. Moreover, evidence indicates that statins, via increased thrombomodulin expression on endothelial cells, may enhance the activity of the protein C anticoagulant pathway. Most of the antithrombotic effects of statins are attributed to the inhibition of isoprenylation of signaling proteins. These novel properties of statins, suggesting that these drugs might act as mild anticoagulants, may explain, at least in part, the therapeutic benefits observed in a wide spectrum of patients with varying cholesterol levels, including subjects with acute coronary events. The HMG-CoA reductase inhibitors (statins) have been shown to exhibit several vascular protective effects, including antithrombotic properties, that are not related to changes in lipid profile. Treatment with statins can lead to a significant downregulation of the blood coagulation cascade, most probably as a result of decreased tissue factor expression, which leads to reduced thrombin generation.
Vascular and Endovascular Surgery, 2010
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, commonly known as statins, are the medical treatment of choice for hypercholesterolemia. In addition to achieving a therapeutic decrease in serum cholesterol levels, statin therapy appears to promote pleiotropic effects that are independent of changes in serum cholesterol. These cholesterol lowering and pleiotropic effects are beneficial not only for the coronary circulation, but for the myocardium and peripheral arterial system as well. Patients receiving statin therapy must be carefully monitored, however, as statins potentially have harmful side effects and drug interactions. This article is part II of a 2-part review, and it focuses on the clinical aspects of statin therapy in cardiovascular disease.