Summary
The paper discusses the controversial attitude regarding the safety of calcium channel blockers (CCBs), especially of the dihydropyridine nifedipine, induced through several meta-analyses of studies with CCBs by Dr. Furberg et al.; as a result, a detrimental effect of CCBs, especially during acute myocardial infarction, has been claimed. Several independent re-analyses of the 16 studies, all performed in the 1980s and mainly using the short-acting nifedipine capsule, did not confirm Furberg's results and showed an insignificant mortality difference between patients on CCBs versus those on control. Nevertheless, new safety studies applying long-acting CCBs (half-lives of 1 or more days) combined with efficacy assessments are necessary, both in hypertension as well as coronary artery disease, to finally clear up this important question.
References
Furberg CD, Psaty BM, Meyer JV. Nifedipine. Doserelated increase in mortality in patients with coronary heart disease. Circulation 1995;92:1326–1331.
Psaty BM, Heckbert SR, Koepsell TD. The risk of myocardial infarction associated with antihypertensive therapies. JAMA 1995;274:620–625.
Kloner RA. Nifedipine in ischemic heart disease. Circulation 1995;92:1074.
Yusuf S. Calcium antagonists in coronary artery disease and hypertension. Time for re-evaluation? Circulation 1995; 92:1079–1082.
Opie LH, Messerli FH. Nifedipine and mortality. Grave defects in the dossier. Editorial. Circulation 1996;92: 1068–1073.
Rafflenbeul W. Nifedipine in acute coronary syndromes. Furberg's refrain revisited. Eur Heart J 1996;17: 1147–1152.
Lichtlen PR, Hugenholtz PG, Rafflenbeul W, Hecker H, Jost S, Deckers JW, and the INTACT group. Retardation of angiographic progression of coronary artery disease by the calcium channel blocker nifedipine—Results of the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT). Lancet 1990;335:1109–1113.
Lichtlen PR. Nifedipine study. Letter to the editor. Circulation 1996;93:1472.
Lichtlen PR, Hugenholtz PG, Rafflenbeul W, Hecker H, Jost S, Nikutta P, Deckers JW. Retardation of the progression of coronary artery disease in man by nifedipine; the INTACT-study (International Nifedipine Trial on Antiatherosclerotic Therapy). Cardiovasc Drugs Ther 1990;4: 1047–1068.
Parmley WW, Nesto RW, Singh BN, Deanfield J, Gottlieb SO, and the N-CAP study group. Attenuation of the circadian patterns of myocardial ischemia with nifedipine GITS in patients with chronic stable angina. J Am Coll Cardiol 1992;19:1380–1389.
Burges RA, Dodd MG. Amlodipine. Cardiovasc Drug Rev 1990;8:25–44.
Lindqvist M, Kahan T, Melcher A, Hjemdahl P. Acute and chronic calcium antagonist treatment elevates sympathetic activity in primary hypertension. Hypertension 1994;24: 287–296.
Rehnquist N, Hjemdahl P, Billing E. Effects of metoprolol versus verapamil in patients with stable angina pectoris. The angina prognosis study in Stockholm (APSIS). Eur Heart J 1996;17:76–81.
Aursnes I, Litleskare I, Froyland H, Abdelnoor M. Association between various drugs used for hypertension and risk of acute myocardial infarction. Blood Pressure 1995;4: 157–163.
Deanfield JE. Effect of amlodipine on the total ischemic burden in patients with chronic stable angina. J Cardiovasc Pharmacol 1995;26(Suppl A):S1-S6.
Packer M. Primary results of the PRAISE trial. Presentation at the American College of Cardiology, 1996;280A: Abstr.
Lichtlen PR. Therapeutic options with the long-acting calcium antagonist amlodipine: Results of the CAPE study. J Cardiovasc Pharmacol 1994;24(Suppl B):S21-S30.
Deanfield JE, Detry JMR, Lichtlen PR, Magnani B, Sellier P, Thaulow E, for the CAPE Study Group. Amlodipine reduced transient myocardial ischemia in patients with coronary artery disease: Double-blind circadian anti-ischemia program in Europe (CAPE Trial). J Am Coll Cardiol 1994; 24:1460–1467.
Lichtlen PR, Lippolt P. Rafflenbeul W, on behalf of the INTACT group investigators. Retardation of angiographic progression of coronary artery disease by nifedipine; the 6-year follow-up study of INTACT (International Nifedipine Trial on Antiatherosclerotic Therapy). J Cardiovasc Pharmacol 1996, in press.
Kiowski W, Erne P, Bertel O, Bolli P, Bühler F. Acute and chronic sympathetic reflex activation and antihypertensive response to nifedipine. J Am Coll Cardiol 1986;7:344–348.
Cohn JN, Levine TB, Olivari MT, et al. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 1984;311:819–823.
Engel HJ, Lichtlen PR. Beneficial enhancement of coronary blood flow by nifedipine. Comparison with nitroglycerin and beta-blocking agents. Am J Med 1981;71:658–666.
Freudenberg H, Lichtlen PR. The normal wall segment in coronary stenoses—a postmortem study. Z Kardiol 1981; 70:863–869.
Rafflenbeul W, Lichtlen PR. Zum Konzept der “dynamischen” Koronarstenose. Z Kardiol 1982;71:439–444.
Antonius TFT, McGregor GA. Contrasting effects of calcium antagonists and angiotensin-converting enzyme inhibitors in patients with high blood pressure. J Cardiovasc Pharmacol 1995;26(Suppl A):S41-S46.
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Lichtlen, P.R. Controversies concerning calcium antagonists. Cardiovasc Drug Ther 10, 409–412 (1996). https://doi.org/10.1007/BF00051104
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DOI: https://doi.org/10.1007/BF00051104