Mechanisms of plaque stabilization for a charged calcium channel blocker in coronary artery disease.
Coronary artery disease (CAD) results from atherosclerosis, a systemic vascular disorder that is the leading cause of death and disability throughout much of the developed world. Because cellular changes associated with vulnerable atherosclerotic plaque are characterized by a loss of normal calcium regulation, there is strong interest in a potential antiatherosclerotic role for calcium channel blockers. This hypothesis has been supported by investigational studies conducted in well-defined cellular and animal models of atherosclerosis. In addition, several clinical studies have tested the benefit of calcium channel blockers among patients with mild-to-moderate CAD. More recent trials have shown reductions in cardiovascular events after treatment with amlodipine, a long-acting, dihydropyridine-type calcium channel blocker. The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) demonstrated that patients with documented CAD treated with amlodipine experienced marked reductions in cardiovascular events compared with patients receiving placebo. Amlodipine also was associated with significant slowing of carotid atherosclerosis, an important surrogate marker for CAD, independent of blood pressure modification. These results have renewed interest in potential plaque stabilization properties of third-generation calcium channel blockers and their possible therapeutic role in CAD.
Mason
R P
RP
Department of Medicine, MCP Hahnemann University School of Medicine, Pittsburgh, Pennsylvania, USA. mason@elucidaresearch.com
D017311:Amlodipine / Q000493:pharmacokinetics* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics* / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000378:metabolism; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D018384:Oxidative Stress; D016032:Randomized Controlled Trials as Topic
D002121:Calcium Channel Blockers; D017311:Amlodipine