Summary
A number of animal studies revealed an inhibition or retardation of the progression of atherosclerosis by calcium-antagonists. Encouraged by these studies, a multicenter trial on the progression of coronary artery disease (CAD) in man was initiated testing the antisclerotic effect of nifedipine against placebo in 426 patients with mild to moderate coronary disease over 3 years. All patients underwent coronary angiography before entering the trial and will be restudied after 3 years; changes of the coronary artery lumen size are quantitatively assessed by a computer-assisted system (CAAS). INTACT (International Trial on Antiatherosclerotic Coronary Therapy) is therefore the first randomized prospective study on the progression of CAD based on a quantitated anigraphic control of the coronary system.
This report presents the design of this still-ongoing study as well as inclusion and exclusion criteria. The quantitative evaluation of the coronary angiograms and the mode of compliance test are described in detail. A number of baseline data as well as the preliminary results of the quantitative evaluation of the first coronary angiograms are presented.
Beside the results on the effect of the calcium-antagonist nifedipine on the progression of CAD, INTACT might also supply information on the antiatherosclerotic potency of other drugs administered additionally (beta-blockers and nitrates) and of HDL-cholesterol.
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References
Henry PD, Bentley K. Suppression of atherosclerosis in cholesterol-fed rabbits treated with nifedipine.J Clin Invest 1981; 68:1966.
Rouleau JL, Parmley WW, Stevens J, et al. Verapamil suppresses atherosclerosis in cholesterol-fed rabbits.J Am Coll Cardiol 1983; 1:1453.
Ginsburg R, Davis K, Bristow MR, et al. Calciumantagonists suppress atherogenesis in aorta but not in the intramural coronary arteries of cholesterol-fed rabbits.Lab Invest 1983; 49:154.
Nayler WG, Dillon JS, Panagiotopoulos S, et al. Dihydropyridines and the ischemic myocardium. In: Lichtlen PR, ed. 6th International Adalat Symposium. Amsterdam: Excerpta Medica 1985; 386–398.
Willis AL, Nagel B, Churchill V, et al. Antiatherosclerotic effects of nicardipine and nifedipine in cholesterol-fed rabbits.Atherosclerosis 1985; 5:250–255.
Sugano M, Nakashima Y, Matsushima T, et al. Suppression of atherosclerosis in cholesterol-fed rabbits by diltiazem injection.Atherosclerosis 1986; 6:237–241.
Hollander W, Paddock J, Nagraj S, et al. Effects of anticalcifying and antifibrotic drugs on preestablished atherosclerosis in the rabbit.Atherosclerosis 1979; 33:111–123.
Blumlein SL, Sievers R, Kidd P, et al. Mechanism of protection from atherosclerosis by verapamil in the cholesterol-fed rabbit.Am J. Cardiol 1984; 54:884.
Fleckenstein A, Fleckenstein-Grün G. Cardiovascular protection by calcium-antagonists.Eur Heart J 1980; 1 (Suppl. B):15.
Fleckenstein A, Frey M, Zorn J, et al. Interdependence of antihypertensive anticalcinotic and antiatherosclerotic effects of calcium-antagonists - model experiments on spontaneously hypertensive rats (SHR). In: Fleckenstein A, van Breemen C, Gross R, Hoffmeister F, eds. Bayer Symposium IX. Cardiovascular Effects of Dihydropyridine-type Calcium-Antagonists and Agonists. Berlin, Heidelberg, New York, Tokyo: Springer-Verlag 1985; 480–499.
Frey M, von Witzleben H, Keidel J, et al. Restriction of calcium-overload of the arterial walls of spontaneously hypertensive rats by calcium-antagonists (verapamil, nifedipine).Naunyn-Schmeid Arch Pharmacol 1980; 313(Suppl):R48.
Van Niekerk JLM, Hendricks T, de Boer HHM, et al. Does nifedipine suppress atherogenesis in WHHL-rabbits?Atherosclerosis 1984; 53:91.
Stender S, Stender I, Nordestgaard B, et al. No effect of nifedipine on atherogenesis in cholesterol-fed rabbits.Atherosclerosis 1984; 4:339–394.
Natio M, Nuauya F, Asai K, et al. Ineffectiveness of calcium-antagonist nifedipine and diltiazem on experimental atherosclerosis in cholesterol-fed rabbits.Angiology 1984; 36:622–627.
Kramsch DM, Chan CT. The effect of agents interfering with soft-tissue calcification and cell proliferation on calcific fibrous-fatty plaques in rabbits.Circ Res 1978; 67:81–89.
Defenders FV. Calcium antagonists and atherosclerosis. Basic studies and therapeutic implications.Life Sci 1983; 32:557–563.
Brensike JF, Lefy JF, Kelsey SF, et al. Effects of therapy with cholestyramine on progression of coronary atherosclerosis: results on the NHLBI-type II coronary intervention study.Circulation 1984; 69:313.
Levy RI, Brensike JF, Epstein STE, et al. The influence of changes in lipid values induced by cholestetyramine and diet on progression of coronary artery disease: results on the NHLBI-type II coronary intervention study.Circulation 1984; 69:325.
Schaefer BJ, Levy RI. Pathogenesis and management of lipoprotein disorders.New Engl J Med 1985; 312:1300.
Artzenius AC, Kromhout D, Barth JD et al. Diet, lipoproteins and the progression of coronary atherosclerosis. The Leiden intervention trial.New Engl J Med 1985; 312:805.
Kushi LH, Lew RA, Stare FJ et al. Diet and 20-year mortality from coronary heart disease.New Engl J Med 1985; 312:811.
Nash DT, Gensini G, Erente P. Effect of lipid-lowering therapy on the progression of coronary atherosclerosis assessed by scheduled repetitive coronary arteriography.Intern J Cardiol 1982; 2:43.
Lichtlen PR, Nellessen U, Rafflenbeul W. In: Lichtlen PR, ed., 6th International Adalat Symposium. Amsterdam: Excerpta Medica 1985; 462–476.
Nellessen U, Rafflenbeul W, Hecker H, et al. Zur Progression der Koronarsklerose. Untersuchungen bei 19 Patienten über 6 Jahre mittels quantitativer Koronarangiographie.Z Kardiol 1984; 73:760.
Reiber JH, Koojman JC, Schlager JC, et al. Computer-assisted analysis of the severity of obstructions from coronary cine-angiograms.Metholod Rev Automed 1984; 5:219.
Nellessen U, Hecker H, Raude E, et al. Riboflavin als Drug-Marker.Die Med Welt 1985; 36:1478–1482.
Bruscke AV, Wijers TS, Colsters W, et al. The anatomic evolution or coronary artery disease demonstrated by coronary arteriography in 256 non-operated patients.Circulation 1981; 63:529–536.
Lichtlen PR, Rafflenbuel W. Progression of coronary artery disease as judged from sequential angiography. In: Hauss WH, Wissler RW, eds. Second Münster International Arteriosclerosis Symposium on Clinical Implications of Recent Research in Atherosclerosis. Opladen: Westdeutscher Verlag 1985; 101.
Kramer JR, Matsuda Y, Mulligan JC, et al. Progression of coronary atherosclerosis.Circulation 1981; 63:519.
Nash DT, Gensini CG, Simon H et al. The Erysichthon Syndrome. Progression of coronary atherosclerosis and dietary hyperlipidemia.Circulation 1977; 56:363.
Okata L, Sakamoto N, Nagano K, et al. Low density lipoprotein-lowering and high density lipoprotein-elevating effects of nicardipine in rats.Biochem Pharmacol 1984; 33:2199.
Chan CT, Wells H, Kramsch DM. Suppression of calcific fibrous-fatty plaque formation in rabbits by agents not affecting elevated serum cholesterol levels.Circ Res 1978; 43:115–125.
Bemis CE, Gorlin R, Kemp HG, et al. Progression of coronary artery disease: a clinical angiographic study.Circulation 1973; 47:455.
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Lichtlen, P.R., Nellessen, U., Rafflenbeul, W. et al. International nifedipine trial on antiatherosclerotic therapy (intact). Cardiovasc Drug Ther 1, 71–79 (1987). https://doi.org/10.1007/BF02125836
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DOI: https://doi.org/10.1007/BF02125836