Calcium-Channel Antagonists for Prevention of Atherosclerosis

Abstract

Spanish

French

OBJECTIVE:

To critically evaluate the current literature regarding the role of calcium-channel antagonists in preventing atherosclerosis.

DATA SOURCES:

English language clinical studies, abstracts, conference proceedings, and review articles pertaining to calcium-channel antagonists and atherosclerosis.

STUDY SELECTION:

Relevant animal and human studies examining the role of calcium-channel antagonists in atherosclerosis prevention and treatment.

DATA EXTRACTION:

Potential mechanisms for the development of atherosclerosis and the use of calcium antagonists for preventing and treating coronary artery disease are discussed. Animal studies are summarized; next, significant data from human clinical studies are presented.

DATA SYNTHESIS:

Available studies are described and discussed.

CONCLUSIONS:

Results from animal and clinical trials in humans suggest that calcium antagonists may retard the development and progression of atherosclerosis. However, most clinical trials to date have been conducted in patients with proven atherosclerotic plaques. Further studies examining the role of calcium-channel antagonists in preventing and treating atherosclerosis are needed, but may be difficult to conduct because of the large numbers of patients required, long trial duration, and associated costs.

Get full access to this article

View all access options for this article.

References

Lipid Research Clinics Program. The Lipid Research Clinics coronary prevention trial results. I. Reduction in incidence of coronary heart disease. JAMA 1984; 251: 358–64.

AHA Conference Report on Cholesterol. Circulation 1989; 80: 715–48.

AHA Task Force on Cholesterol Issues. The cholesterol facts. A summary of the evidence relating dietary fats, serum cholesterol, and coronary heart disease. Circulation 1990; 81: 1721–33.

Fuster

Badimon

Chesebro

. The pathogenesis of coronary artery disease and the acute coronary syndromes (second of two parts). N Engl J Med 1992; 326: 310–8.

Fuster

Badimon

Taubman

Chesebro

. Syndromes of accelerated atherosclerosis: Role of vascular injury and smooth muscle cell proliferation. J Am Coll Cardiol 1990; 15: 1667–8.

Barath

Fishbein

Cao

Berenson

Helfant

Forrester

. Detection and localization of tumor necrosis factor in human atheroma. Am J Cardiol 1990; 65: 297–302.

Hansson

Jonasson

Seifert

Stemme

. Immune mechanisms in atherosclerosis. Arteriosclerosis 1989; 9: 567–78.

Fuster

Badimon

Chesebro

. The pathogenesis of coronary artery disease and the acute coronary syndromes (first of two parts). N Engl J Med 1992; 326: 242–50.

Parmley

. Vascular protection from atherosclerosis: Potential of calcium antagonists. Am J Cardiol 1990; 66: 161–221.

10.

Ross

Glomset

. The pathogenesis of atherosclerosis. N Engl J Med 1976; 295: 369–77, 420–5.

11.

Ross

. The pathogenesis of atherosclerosis—an update. N Engl J Med 1986; 314: 488–99.

12.

Weinstein

Heider

. Antiatherogenic properties of calcium antagonists: State of the art. Am J Med 1989; 86 (suppl 4A):27–32.

13.

Henry

. Antiatherosclerotic effects of calcium antagonists: A brief review. Clin Invest Med 1987; 10: 601–5.

14.

Levy

Lian

Gallop

. Atherocalcin: A gamma-carboxyglutamic acid-containing protein from atherosclerotic plaque. Biochem Biophys Res Commun 1979; 71: 41–8.

15.

Fleckenstein

Fleckenstein-Grun

. Cardiovascular protection by calcium antagonists. Eur Heart J 1980; 1 (suppl 8):15–21.

16.

Bernini

Catapano

Corsini

Furnagalli

Paoletti

. Effects of calcium antagonists on lipids and atherosclerosis. Am J Cardiol 1989; 64: 129–34.

17.

Keogh

Schroeder

. A review of calcium antagonists and atherosclerosis. J Cardiovasc Pharmacol 1990; 16 (suppl 6):S28–35.

18.

Dougherty

Roteri

Schonfeld

Sobel

. Inhibition of cholesterol ester deposition in macrophages by calcium entry blockers: An effect dissociated from calcium entry blockade. Br J Pharmacol 1987; 91: 113–8.

19.

Entigin

Hajjar

. Calcium channel blockers enhance cholesterol ester hydrolysis and decrease total cholesterol accumulation in human aortic tissue. Circ Res 1990; 66: 185–90.

20.

Stehbens

. The lipid hypothesis and the role of hemodynamics in atherogenesis. Prog Cardiovasc Dis 1990; 33: 119–36.

21.

Ram

CVS

. Antiatherosclerotic and vasculoprotective actions of calcium antagonists. Am J Cardiol 1990; 66: 291–321.

22.

Weinstein

Heider

. Antiatherogenic properties of calcium antagonists. Am J Cardiol 1987; 59 (suppl): 163B–72B.

23.

Henry

Bentley

. Suppression of atherogenesis in cholesterol-fed rabbit treated with nifedipine. J Clin Invest 1981; 68: 1366–9.

24.

Panagiotopoulos

Nayler

. Calcium antagonists and the suppression of atherosclerosis (abstract). J Mol Cell Cardiol 1984; 16: XIV.

25.

Willis

Nagel

Churchill

Whyte

Smith

Mahmud

. Antiatherosclerotic effects of nicardipine and nifedipine in cholesterol-fed rabbits. Arteriosclerosis 1985; 5: 250–5.

26.

Watanabe

Ishikawa

Mukodani

Miyazaki

Tsukitani

Takanos

. Nifedipine suppresses atherosclerosis in cholesterol-fed rabbits but not in WHHL-rabbits (abstract). Circulation 1985; 72 (suppl III):281.

27.

Habib

Bossaler

Wells

Williams

Morrisett

Henry

. Preservation of endothelium-dependent vascular relaxation in cholesterol-fed rabbit by treatment with the calcium blocker PN-200-110. Circ Res 1986; 58: 305–9.

28.

Heider

Weinstein

Pickens

Lan

. Anti-atherogenic activity of the calcium channel blocker PN-200-110 (isradipine): A novel effect on matrix synthesis independent of calcium channel blockade. Transplant Proc 1987; 19: 96–109.

29.

Fronek

. Effect of nisoldipine on diet induced atherosclerosis in rabbits. Ann N Y Acad Sci 1988; 522: 525–6.

30.

Blumlein

Sievers

Kidd

Parmley

. Mechanism of protection from atherosclerosis by verapamil in the cholesterol-fed rabbit. Am J Cardiol 1984; 54: 884–9.

31.

Rouleau

Parmley

Stevens

Wikman-Coffelt

Sievers

Mahley

. Verapamil suppresses atherosclerosis in cholesterol-fed rabbits. J Am Coll Cardiol 1983; 1: 1453–60.

32.

Ginsburg

Davis

Bristow

McKennett

Kodsi

Billingham

. Calcium antagonists suppress atherogenesis in aorta but not in the intramural coronary arteries of cholesterol-fed rabbits. Lab Invest 1983; 49: 154–8.

33.

Sugano

Nakashima

Matsushima

Takahara

Takasugi

Kuroiwa

. Suppression of atherosclerosis in cholesterol-fed rabbits by diltiazem injection. Arteriosclerosis 1986; 6: 237–41.

34.

Stender

Stende

Nordestgaard

Kjeldsen

. No effect of nifedipine on atherogenesis in cholesterol-fed rabbits. Arteriosclerosis 1984; 4: 389–94.

35.

Naito

Kuzuya

Asai

Shibata

Yoshimine

. Ineffectiveness of Ca²⁺-antagonists nicardipine and diltiazem on experimental atherosclerosis in cholesterol-fed rabbits. Angiology 1984; 35: 622–7.

36.

Fleckenstein-Grün

Fleckenstein

. Antiarteriosclerotic aspects of calcium antagonists (abstract). In: Proceedings of the Second International Symposium on Calcium Antagonists in Cardiovascular Care; 1991 Feb 13–15; Basel. Stamford, CT: PRO Communications, 1991: 19.

37.

Thimm

Frey

Fleckenstein-Grün

Fleckenstein

. Lack of identity of experimental coronary plaques in cholesterol-fed rabbits with spontaneous arteriosclerotic lesions in humans (abstract). In: Proceedings of the Second International Symposium on Calcium Antagonists in Cardiovascular Care; 1991 Feb 13–15; Basel. Stamford, CT: PRO Communications, 1991: 85.

38.

Kober

Schneider

Kaltenbach

. Can the progression of coronary sclerosis be influenced by calcium antagonists? J Cardiovasc Pharmacol 1989; 13 (suppl 4):S2–6.

39.

Lichtlen

Hugenholtz

Rafflenbeul

Hecker

Jost

Decker

. Retardation of angiographic progression of coronary artery disease by nifedipine. Results of the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT). Lancet 1990; 335: 1109–13.

40.

Waters

Lesperance

Francetich

Lemarbre

Dyrda

Havel

. Design features of a controlled clinical trial to assess the effect of a calcium antagonist upon the progression of coronary artery disease. Controlled Clin Trials 1987; 8: 216–42.

41.

Waters

Lesperance

Francetich

Theroux

Reitman

Hudon

. A controlled clinical trial to assess the effect of a calcium antagonist upon the progression of coronary atherosclerosis (abstract). Circulation 1989; 80 (suppl 11):266.

42.

Schneider

Kober

Roebruck

Noack

Alle

Cieslinski

. Retardation of development and progression of coronary atherosclerosis: A new indication for calcium antagonists? Eur J Clin Pharmacol 1990; 39 (suppl 1):S17–23.

43.

Grimm

Flack

Byington

Bond

Brugger

. A comparison of antihypertensive drug effects on the progression of extracranial carotid atherosclerosis: The Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). Drugs 1990; 40 (suppl 2):38–43.

44.

Furberg

Byington

, Borhani NA, for the MIDAS Research Group. Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). Am J Med 1989; 86 (suppl 4A):37–9.

45.

Loaldi

Polese

Montorsi

De Cesare

Fabbiocchi

Ravagnani

. Comparison of nifedipine, propranolol and isosorbide dinitrate on angiographic progression and regression of coronary arterial narrowings in angina pectoris. Am J Cardiol 1989; 64: 433–9.

46.

Schroeder

. The progression of atherosclerosis in the transplant model (abstract). In: Proceedings of the International Summit on Diltiazem HCl: A Decade of Experience. 1991 May 23–26; The Hague, 1991: 18.

47.

Fowler

Schroeder

Gao

S-Z

Valantine

Alderman

Hunt

. Vascular protection: influence of diltiazem on accelerated graft atherosclerosis in heart transplantation (abstract). In: Proceedings of the Second International Symposium on Calcium Antagonists in Cardiovascular Care; 1991 Feb 13–15; Basel. Stamford, CT: PRO Communications, 1991.

48.

Bond

Wilmoth

Enevold

Strickland

. Detection and monitoring of asymptomatic atherosclerosis in clinical trials. Am J Med 1989; 86 (suppl 4A):33–6.

49.

Miller

. Long-term complications of cardiac transplantation. Prog Cardiovasc Dis 1991; 33: 229–82.