Long term effects of nisoldipine on the progression of coronary atherosclerosis and the occurrence of clinical events: the NICOLE study

Abstract

Background: Earlier angiographic studies have suggested that calcium antagonists may prevent the formation of new coronary lesions and the progression of minimal lesions. Conversely, a meta-analysis suggested that these drugs may increase cardiovascular mortality and morbidity in patients with coronary heart disease. Objective: To investigate whether nisoldipine retards the progression of coronary atherosclerosis or reduces the occurrence of clinical events. Design and setting: The NICOLE study (NIsoldipine in COronary artery disease in LEuven) is a single centre, randomised, double blind, placebo controlled trial with coronary angiography at baseline, six months, and three years of follow up. Patients: 826 patients who had undergone successful coronary angioplasty were randomised to nisoldipine 40 mg once daily or placebo. The intention to treat and per protocol population consisted of 819 and 578 patients, respectively. Results: In the per protocol population, 625 of the nisoldipine treated and 655 of the placebo treated patients (NS) showed angiographic progression in at least one coronary arterial segment, defined as an increase in diameter stenosis of > 13%. The average minimum luminal diameter of the non-dilated lesions decreased by 0.163 mm and 0.167 mm in the nisoldipine and placebo groups, respectively (NS). The respective numbers of new lesions detected were 7 and 13 (NS). In the intention to treat population, the rates of death, stroke, and acute myocardial infarction were similar in both treatment groups. However, nisoldipine use was associated with fewer revascularisation procedures and thus the percentage of patients with any clinical event was lower (44.6% v 52.6%, p = 0.02). Conclusions: Nisoldipine has no demonstrable effect on the angiographic progression of coronary atherosclerosis or the risk of major cardiovascular events but its use is associated with fewer revascularisation procedures.

Blood Pressure Reduction and Cardiovascular Prevention: An Update Including the 2003-2004 Secondary Prevention Trials

“…Among the 5 trials of dihydropyridine calcium-channel blockers (35,41,43,44,47), there was no heterogeneity in the results with regard to stroke (p= 0.81), myocardial infarction (p= 0.16) and the composite of all cardiovascular events, which also included procedures and revascularization (p= 0.52). The pooled odds ratios were: 0.71 (CI, 0.55−0.92; p= 0.0015), 0.97 (CI, 0.83−1.13; p= 0.70), and 0.78 (CI, 0.72−0.85; p< 0.0001), respectively.…”

“…In 5 trials with 12,342 randomized patients (Table 2), the experimental agent was a dihydropyridine calcium-channel blocker: amlodipine in CAMELOT/Aml (41), PREVENT (42,43), and IDNT2 (33−35); nifedipine GITS (gastro-intestinal therapeutic system) in ACTION (44,45); and nisoldipine in NICOLE (46,47). In 9 trials with 43,227 randomized patients ( (57); and trandolapril in PEACE (58).…”

Randomized Controlled Trials of Blood Pressure Lowering in Hypertension

“…26 The design of BP-lowering RCTs comparing calcium antagonists, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers with placebo (with tested drugs and placebo often being added on a background of pre-existing antihypertensive therapy) was such that smaller SBP/ DBP differences were achieved. Nonetheless, evidence of significant reductions of stroke, major cardiovascular events, and cardiovascular and all-cause deaths by 10 RCTs (30 359 patients) comparing calcium antagonists with placebo 28,32,35,41,54,55,66,70,85,90 ( Figure 3D), evidence of significant reductions of stroke, CHD, HF, and major cardiovascular events by 12 RCTs (35 707 patients) using angiotensin-converting enzyme inhibitors 32,42,48,66,73,76,77,79,81,83,88,92 ( Figure 3E), and evidence of significant reductions in stroke, HF, and major cardiovascular events by 13 RCTs (65 256 patients) using angiotensin receptor blockers 49,75,80,82,[85][86][87]89,91,[93][94][95][96] ( Figure 3F) were obtained. 26 Among calcium antagonist RCTs, it was possible to separately analyze, in a sensitivity meta-analysis, 4 RCTs 35,41,54,55 enrolling exclusively hypertensive patients without or with mini...…”

Effect of Statins and Calcium Channel Blockers on All-Cause Mortality and Cardiovascular and Cerebrovascular Disease Mortality in 958 Chinese Hospitalized Patients with Peripheral Arterial Disease after 13 Months of Follow-up

“…However, several trials have also indicated that CCBs did not increase the risk of death. [32][33][34][35] In our study, we found that CCBs can reduce the allcause mortality and cardiovascular and cerebrovascular mortality rate in patients with PAD. Hypertension is the major risk factor for PAD, and control of the blood pressure is an important step in prevention.…”