Antiatherothrombotic properties of statins: implications for cardiovascular event reduction

JAMA. 1998 May 27;279(20):1643-50. doi: 10.1001/jama.279.20.1643.

Abstract

Clinical trials of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statin therapy have demonstrated that baseline or treated low-density lipoprotein (LDL) cholesterol levels are only weakly associated with net coronary angiographic change or cardiovascular events. The beneficial effects of statins on clinical events may involve nonlipid mechanisms that modify endothelial function, inflammatory responses, plaque stability, and thrombus formation. Experimental animal models suggest that statins may foster stability through a reduction in macrophages and cholesterol ester content and an increase in volume of collagen and smooth muscle cells. The thrombotic sequelae caused by plaque disruption is mitigated by statins through inhibition of platelet aggregation and maintenance of a favorable balance between prothrombotic and fibrinolytic mechanisms. These nonlipid properties of statins may help to explain the early and significant cardiovascular event reduction reported in several clinical trials of statin therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antithrombins / pharmacology*
  • Antithrombins / therapeutic use
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol, LDL / blood*
  • Cholesterol, LDL / physiology
  • Clinical Trials as Topic
  • Coronary Disease / blood
  • Coronary Disease / prevention & control
  • Endothelium, Vascular / physiology*
  • Fibrinogen
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypolipidemic Agents / pharmacology*
  • Hypolipidemic Agents / therapeutic use
  • Inflammation
  • Lovastatin / pharmacology
  • Lovastatin / therapeutic use
  • Muscle, Smooth, Vascular / physiology
  • Platelet Aggregation*
  • Pravastatin / pharmacology
  • Pravastatin / therapeutic use
  • Simvastatin / pharmacology
  • Simvastatin / therapeutic use
  • Thromboplastin
  • Thrombosis / physiopathology

Substances

  • Antithrombins
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Fibrinogen
  • Thromboplastin
  • Lovastatin
  • Simvastatin
  • Pravastatin