Mechanisms of plaque stabilization for the dihydropyridine calcium channel blocker amlodipine: review of the evidence.
Coronary artery disease (CAD) is the consequence of atherosclerosis, a vascular disorder that is the leading cause of death and disability throughout much of the developed world. Certain cellular changes in the vulnerable atherosclerotic plaque are characterized by a loss of normal calcium regulation. This observation has led to interest in a potential antiatherogenic role for calcium channel blockers (CCBs), independent of their effects on vasodilation. The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) demonstrated that treatment with amlodipine, a third-generation CCB, in patients with documented CAD produced marked reductions in cardiovascular events as compared with placebo, without a reduction in coronary luminal loss. Amlodipine therapy was also associated with significant slowing in carotid atherosclerosis, an important surrogate marker for CAD, independent of blood pressure changes. The findings from PREVENT were remarkably consistent with another study known as the Coronary Angioplasty Amlodipine Restenosis Study (CAPARES). A reduction in the progression of carotid atherosclerosis has also been recently reported for lacidipine, another third-generation dihydropyridine CCB. These clinical findings have led to a renewed interest in potential plaque stabilization properties of certain CCBs, as will be systematically reviewed in this article. It is also probable that vascular protective agents, such as amlodipine may work in a synergistic fashion with other established treatments, including HMG-CoA reductase inhibitors, to effectively improve outcomes in patients who are at risk for or have established CAD.
Mason
R Preston
RP
Membrane Biophysics Laboratory, Division of Cardiology, Department of Medicine and Biochemistry, MCP Hahnemann University School of Medicine, Allegheny Campus, Pittsburgh, PA, USA. rpmason@elucidaresearch.com
D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000188:drug therapy; D004730:Endothelium, Vascular / Q000378:metabolism; D015870:Gene Expression; D006321:Heart / Q000187:drug effects; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
D002121:Calcium Channel Blockers; D017311:Amlodipine