Design features of a controlled clinical trial to assess the effect of a calcium entry blocker upon the progression of coronary artery disease

Waters, David D.; Freedman, Donna; Lespérance, Jacques; Théroux, Pierre; Lemarbre, L; Kamm, Barbara; Joyal, Michel; Dyrda, Ihor; Gosselin, Gilbert; Hudon, Gilles; Hache, Marilyn; Halloran, Judith; Havel, Richard J.

doi:10.1016/0197-2456(87)90046-8

Cited by 35 publications

(5 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using the criterion of a minimum diameter decrease of 0.4 mm or more, 12 of 99 nicardipine patients and 28 of 118 placebo patients had progression of at least one stenosis of 20% or less (12% versus 24%, p=0.035); 7.3% (13 of 178) of nicardipine lesions and 14.2% (33 of 233) of placebo lesions progressed (p=0.039). Using the criterion of a percent stenosis increase of 10% or more, 15 nicardipine patients (15%) and 32 placebo patients (27%) had progression (p=0.046); 9.0% of stenoses of 20% or less in nicardipine-treated patients and 16.3% of such lesions in placebo-treated patients progressed (p=0.038).…”

Section: Progression Of Coronary Stenoses Of 20% or Lessmentioning

confidence: 99%

See 1 more Smart Citation

A controlled clinical trial to assess the effect of a calcium channel blocker on the progression of coronary atherosclerosis.

et al. 1990

View full text Add to dashboard Cite

To determine whether calcium channel blockers influence the progression of coronary atherosclerosis, 383 patients age 65 years or less with 5-75% stenoses in at least four coronary artery segments were selected at random within 1 Ninety-two nicardipine patients (55%) and 95 placebo patients (57%) had progression at one or more sites (p=NS). Regression, that is, an improvement by l1o0 or more in diameter stenosis, was seen in 140 of 2,323 lesions (6.0%) overall, with no significant intergroup difference. Among the 217 patients with 411 stenoses of 20% or less in the first study, such minimal lesions progressed in only 15 of 99 nicardipine patients compared with 32 of 118 placebo patients (15% versus 27%, p =0.046). In this subgroup, 16 of 178 minimal lesions in nicardipine patients and 38 of 233 minimal lesions in placebo patients progressed (p=0.038). By stepwise logisticregression analysis, baseline systolic blood pressure (p=0.04) and the change in systolic blood pressure between baseline and 6 months (p=0.002) correlated with progression of minimal lesions. This suggested blood pressure reduction may account for the beneficial action of nicardipine. These results suggested nicardipine has no effect on advanced coronary atherosclerosis but may retard the progression of minimal lesions. (Circulation 1990;82:1940-1953 Several calcium channel blockers have been shown to retard the development of athero-1, sclerosis in rabbits fed cholesterol-rich diets.1-7 The mechanism through which these drugs exert their antiatherogenic effects is not known, but is being From the

show abstract

Section: Progression Of Coronary Stenoses Of 20% or Lessmentioning

confidence: 99%

“…The details of data collection at each visit and data management have been described. 12 Compliance to use of study medication was monitored by a capsule count at each visit and by measurements of plasma nicardipine levels 1-3 hours postdose. Compliance averaged greater than 90% at each visit by capsule count.…”

Section: Study Protocolmentioning

confidence: 99%

A controlled clinical trial to assess the effect of a calcium channel blocker on the progression of coronary atherosclerosis.

et al. 1990

View full text Add to dashboard Cite

show abstract

“…In 1987 a prospective, randomized study in 383 patients with angiographically proven coronary artery disease was initiated by the Montreal Heart Institute [45]. Patients eligible for this study had to show clinical and angiographical parameters which suggested a high likelihood of progression of atherosclerosis.…”

Section: Retrospective Analysismentioning

confidence: 99%

Retardation of development and progression of coronary atherosclerosis: a new indication for calcium antagonists?

Schneider

Kober

Roebruck

et al. 1990

Eur J Clin Pharmacol

View full text Add to dashboard Cite

Development of atherosclerotic lesions in animals, preferrably induced by a high-cholesterol diet, can be successfully suppressed by calcium channel blockers such as verapamil, nifedipine, nicardipine and diltiazem. The issue of a beneficial effect of calcium channel blockers on human coronary atherosclerosis is however not yet settled. At present, three prospective randomized clinical trials with calcium channel blockers (Nifedipine, Verapamil, Nicardipine) are being conducted (INTACT, FIPS, Study of the Montreal Heart Institute). Target variable for assessment of progression in these studies is the severity of coronary atherosclerosis evaluated by angiography both at entry into the study and after 2-3 years of treatment. A total of 445 patients after coronary bypass surgery (CABG) were entered in FIPS (Frankfurt Isoptin Progression Study) and randomly allocated to either verapamil 120 mg t.i.d. or placebo. The extent of coronary atherosclerosis is assessed by repeat angiography both 1 year and 3 years after randomization. Three vessel regions are evaluated separately. 1. Native vessels without bypass grafts and segments distal to the peripheral graft anastomosis ("core region") 2. Segments bridged by bypass grafts and 3. Bypass grafts. The 1-year follow-up was completed by 162 patients (Group A = 80 patients; Group B = 82 patients). There was a homogeneous distribution in the two groups for all clinical variables, graft patency rates, and the incidence of clinical events (myocardial infarction, need for cardiac surgery or PTCA, cardiac death). The overall progression rate of atherosclerosis in the first year was expectedly low.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

“…It has been reported that calcium channel blockers suppress atherogenesis in cholesterol-fed animals (1-3) and the development of new occlusive lesions in pa tients with coronary atherosclerosis (4,5). The possible mechanisms of this antiatherogenic effect are probably related to lowering of arterial pressure, prevention of dyslipidemic endothelial injury and inhibition of arterial smooth muscle cell (SMC) proliferation (6).…”

mentioning

confidence: 99%

Effect of Manidipine on Balloon Catheter-Induced Arterial Smooth Muscle Cell Proliferation in Spontaneously Diabetic GK Rats

Odaka

Nagano

Miki

et al. 1992

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-The inhibitory effect of manidipine, a long acting calcium channel blocker, on vascular smooth muscle cell proliferation was investigated in spontaneously diabetic GK rats with balloon catheter-induced denudation of the carotid artery. Treatment with manidipine at doses of 4.6 and 15.1 mg/kg/day inhibited thickening of the neo-intima in the balloon catheter-injured artery without any effect on blood pressure and lowered the ratio of intima to wall areas and wall to total vascular areas in a dose-dependent fashion. These results suggest that manidipine inhibits an abnormal proliferation of the intima in the carotid artery of spontaneously diabetic rats.Keywords: Manidipine, Neo-intima, Antimyoproliferative actionIt has been reported that calcium channel blockers suppress atherogenesis in cholesterol-fed animals (1-3) and the development of new occlusive lesions in pa tients with coronary atherosclerosis (4, 5). The possible mechanisms of this antiatherogenic effect are probably related to lowering of arterial pressure, prevention of dyslipidemic endothelial injury and inhibition of arterial smooth muscle cell (SMC) proliferation (6). In this paper, we examined the effects of manidipine, a long acting calcium channel blocker (7), on SMC prolifera tion after vascular injury induced by a balloon catheter in spontaneously diabetic Goto-Kakizaki (GK) rats (8), in which severe thickening of intima in the injured artery is observed.Male spontaneously diabetic GK rats were bred in our Laboratory Animal Unit. They were housed in in dividual wire cages and fed a commercial stock diet (CE-2, Clea Japan Inc., Tokyo) in a room with control led temperature (23 ± 1°C), humidity (55 ± 5%) and lighting (08:00-20:00).Thirteen-week-old, male GK rats were given a pow dered CE-2 diet with or without manidipine at a con centration (w/w) of 0.01 or 0.03% for 20 days. The concentrations were selected as those producing slight and mild antihypertensive effects in spontaneously hypertensive rats (9). The drug intake was calculated from the food intake and expressed as mg/kg/day. On day 6, these rats were anesthetized with pentobarbital (50 mg/kg, i.p.) and subjected to balloon catheter-in duced denudation of the left carotid artery according to the method described by Baumgartner (10). In brief, a 2F balloon catheter (Edwards Laboratories, Santa Ana, CA) was introduced into the left carotid artery via the left femoral artery. The balloon was then inflated with saline and drawn back and forth 3 times over a distance of 1 to 1.5 cm to remove the endothelium of the carotid artery. On day 20, the systolic blood pressure was measured by a tail pulse pick-up method in unanesthe tized rats. Thereafter, a catheter was inserted into the ascending aorta via the left ventricle under pentobarbi tal anesthesia. Phosphate-buffered saline with 4% form aldehyde (pH 7.4) was perfused under a pressure of 90 to 100 mmHg for 10 min to fix the carotid artery. Five frozen cross-sections (12 gum in thickness) from each injured artery were stained with ...

show abstract

Design features of a controlled clinical trial to assess the effect of a calcium entry blocker upon the progression of coronary artery disease

Cited by 35 publications

References 38 publications

A controlled clinical trial to assess the effect of a calcium channel blocker on the progression of coronary atherosclerosis.

A controlled clinical trial to assess the effect of a calcium channel blocker on the progression of coronary atherosclerosis.

Retardation of development and progression of coronary atherosclerosis: a new indication for calcium antagonists?

Effect of Manidipine on Balloon Catheter-Induced Arterial Smooth Muscle Cell Proliferation in Spontaneously Diabetic GK Rats

Contact Info

Product

Resources

About