Concept of an antiatherosclerotic efficacy of calcium entry blockers

Abstract

Animal experiments suggest an inhibitory effect of calcium entry blockers on arterial calcinosis and the formation of atherosclerotic plaques. Experiments with isolated tissues suggest various mechanisms for an antiatherosclerotic effect of calcium entry blockers. INTACT, the International Nifedipine Trial on Antiatherosclerotic Therapy, is the first study investigating, with a prospective, placebo-controlled, randomized, double-blind design, the influence of a calcium entry blocker (nifedipine 80 mg/day) on the progression of coronary atherosclerosis in patients with proven coronary artery disease. Study endpoints were changes of established coronary stenoses (diameter reduction greater than or equal to 20%), as well as the formation of new stenoses as documented by coronary angiography. Standardized coronary angiograms were taken before and after a treatment period of 3 years. The angiograms were quantitatively analyzed with the computer-assisted edge detection system CAAS. Of the 425 patients included in the study, 282 patients (134 on nifedipine and 148 on placebo) revealed no protocol violations. In the inclusion angiograms of these patients, 893 coronary stenoses were detected which were not significantly influenced in their development by nifedipine. However, 196 entirely new coronary lesions, 185 stenoses and 11 occlusions, were found in the follow-up angiograms. There were 78 lesions in 54 patients (40%) on nifedipine (0.58 new lesions/patient) and 118 lesions in 73 patients (49%; n.s.) on placebo (0.8 new lesions/patient; p = 0.031). In two other studies on the inhibiting effect of dihydropyridine calcium entry blockers on the progression of coronary artery disease in man defining angiographic endpoints, the drugs were also shown to reduce the number of newly formed significant coronary lesions. If further trials in man confirm a protective role of calcium entry blockers against the formation of atherosclerotic coronary lesions, a new strategy in the prevention of coronary artery disease has to be considered.

Effect of a Dihydropyridine-Type Calcium Channel Blocker on Vascular Remodelling after Experimental Balloon Angioplasty

“…The increase in the cross sectional area was accompanied by a reduced cell count in the different layers of the vessel wall ( Table 2) and although we could not show a reduced cellular proliferation in the treatment group after 3 days a reduced number of SMC layers in the neointima 28 days after BA compared with placebo animals could be detected. Many studies show a beneficial effect of calcium antagonists on the progression of atherosclerosis [21,22]. In animal models various calcium antagonists modified neointimal hyperplasia.…”

Abdominal aortic calcification: from ancient friend to modern foe

“…74,75 Some small clinical trials have confirmed these results in the coronary arteries in humans. In placebo-controlled trials, nifedipine was shown to reduce the number of newly formed coronary lesions in early stage coronary artery disease, 76 but not instable angina pectoris, 77 and to slow down coronary artery calcification when compared to co-amizolide in patients with hypertension. 78 Azelnidipine compared to the diuretic indapamide was shown to improve arterial stiffness in patients with hypertension.…”