Effect of Amlodipine on the Progression of Atherosclerosis and the Occurrence of Clinical Events

Abstract

Background-The results of angiographic studies have suggested that calcium channel-blocking agents may prevent new coronary lesion formation, the progression of minimal lesions, or both. Methods and Results-The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) was a multicenter, randomized, placebo-controlled, double-masked clinical trial designed to test whether amlodipine would slow the progression of early coronary atherosclerosis in 825 patients with angiographically documented coronary artery disease. The primary outcome was the average 36-month angiographic change in mean minimal diameters of segments with a baseline diameter stenosis of 30%. A secondary hypothesis was whether amlodipine would reduce the rate of atherosclerosis in the carotid arteries as assessed with B-mode ultrasonography, which measured intimal-medial thicknesses (IMT). The rates of clinical events were also monitored. The placebo and amlodipine groups had nearly identical average 36-month reductions in the minimal diameter: 0.084 versus 0.095 mm, respectively (Pϭ0.38). In contrast, amlodipine had a significant effect in slowing the 36-month progression of carotid artery atherosclerosis: the placebo group experienced a 0.033-mm increase in IMT, whereas there was a 0.0126-mm decrease in the amlodipine group (Pϭ0.007). There was no treatment difference in the rates of all-cause mortality or major cardiovascular events, although amlodipine use was associated with fewer cases of unstable angina and coronary revascularization. Conclusions-Amlodipine has no demonstrable effect on angiographic progression of coronary atherosclerosis or the risk of major cardiovascular events but is associated with fewer hospitalizations for unstable angina and revascularization.

The Phase III, double-blind, parallel-group controlled study of amlodipine 10 mg once daily in Japanese patients with essential hypertension who insufficiently responded to amlodipine 5 mg once daily

“…Moreover, calcium antagonists have been found to possess blocking activity on arteriosclerosis progression. 16 Approximately 60% of patients with essential hypertension who were undergoing treatment with antihypertensive drugs including amlodipine failed to achieve the target BP levels that were stipulated by the 2000 JSH guidelines. 2 As guidelines for the management of hypertension in the United States, 17 Europe 18 and Japan established the more strict control of BP in hypertensive patients, greater needs to demonstrate evidence for uptitrating amlodipine from 5 to 10 mg once daily were generated.…”

A randomized, double-blind, four-arm parallel-group study of the efficacy and safety of azelnidipine and olmesartan medoxomil combination therapy compared with each monotherapy in Japanese patients with essential hypertension: the REZALT study

“…8,9 Similarly, dihydropyridine CCBs might have organ-protective effects (that is, regression of left ventricular hypertrophy or inhibition of the progression of atherosclerosis). 10,11 The ACCOMPLISH study demonstrated that treatment with an angiotensin-converting enzyme inhibitor plus a CCB was associated with a 20% reduction in cardiovascular morbidity and mortality in high-risk patients, relative to angiotensin-converting enzyme inhibitor/diuretic therapy. 12 These findings suggest that the combination of a renin-angiotensin system inhibitor and a CCB may be effective in preventing cardiovascular events.…”

The Effect of Losartan and Amlodipine on Left Ventricular Diastolic Function and Atherosclerosis in Japanese Patients with Mild-to-Moderate Hypertension (J-ELAN) study

“…In the previous studies of the Western countries, the administration of amlodipine 31,32 or losartan 33,34 decreased IMT. In this study with Japanese patients, amlodipine significantly increased IMT and losartan did not change it, although both decreased blood pressure.…”