[Effects of calcium antagonists on atherosclerosis progression and intima media thickness].
Calcium antagonists are currently considered first-choice agents for treating hypertension. They are also active antianginal drugs. Their protective effects against ischaemia and their antiatherogenic potential, which have been demonstrated in various experimental models, may contribute to their preventive effect against the early atherosclerotic processes. However, their effects on survival and cardiovascular events have been inconsistent and controversial. Recent studies have suggested that mortality may be increased by short-acting agents. The effects of certain long-acting calcium antagonists may be different. In early clinical trials, nifedipine and nicardipine did not alter the progression of significant coronary artery narrowing, but did reduce the development of new atherosclerotic lesions. Nevertheless, the number of cardiovascular events was not decreased. The Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) showed a higher incidence of angina and more frequent cardiovascular events in patients treated with isradipine. In the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT), after 3 years' follow-up, progression of significant atherosclerotic lesions and the development of new lesions were not significantly altered by treatment with amlodipine. However, it would appear that quantitative angiography may not be appropriate for monitoring the progression of atherosclerosis. Because of arterial remodelling, angiographic images may not show changes in the arterial lumen, in arteries where intravascular ultrasound may detect important atherosclerotic plaques. High resolution B-mode ultrasonography of the carotid artery may be more informative, since carotid intima media thickness is strongly correlated with cardiovascular risk factors, the prevalence of cardiovascular disease, and the presence of atherosclerotic lesions at other arterial sites. In the PREVENT trial, carotid ultrasonography showed that intima media thickness was stabilised in the amlodipine group, while progression was uninterrupted in the placebo group. The mechanism of amlodipine in slowing the progression of intima media thickness may be related to its antiatherogenic effect, as well as to its effect on cellular growth and hyperplasia of the arterial wall. It is interesting to note that, as a secondary objective of the PREVENT trial, patients treated with amlodipine had fewer ischaemic events than those treated with placebo. The beneficial effects of amlodipine on arterial thickening and on the prevention of ischaemic events suggest that amlodipine may be recommended for the management of all patients with stable angina. A larger trial with a longer follow-up period should be performed in order to confirm the promising results of PREVENT.
Zannad
F
F
Centre d'Investigations Cliniques INSERM-CHU, Nancy, France. f.zannad@chu-nancy.fr
D017311:Amlodipine / Q000494:pharmacology* / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D018450:Disease Progression; D004452:Echocardiography; D006801:Humans; D017202:Myocardial Ischemia / Q000517:prevention & control; D012107:Research Design; D017539:Tunica Intima / Q000033:anatomy & histology* / Q000187:drug effects
D002121:Calcium Channel Blockers; D017311:Amlodipine