Use of Calcium Antagonists After Myocardial Infarction: Focus on the DEFIANT Studies

Conference paper


The potential advantages of calcium antagonists in patients recovering from acute myocardial infarction include their potent systemic and coronary vasodilator properties, the anti-arrhythmic properties of drugs such as verapamil and diltiazem, and the possible beneficial effect of calcium channel blocking drugs on myocardial calcium handling and ventricular diastolic function [1]. To minimize the myocardial depressant effect which characterized the first-generation calcium antagonists [2–5], second and third-generation vasoselective drugs with enhanced safety profile and a longer duration of action were developed [6]. The newer calcium antagonists may be associated with a more favorable neurohormonal profile [7–9].


Acute Myocardial Infarction Calcium Antagonist Diastolic Ventricular Function Secondary Prevention Reinfarction Israeli Nifedipine Trial Ventricular Loading Condition 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Lorell BH, Paulus WJ, Grossman W, Wynne J, Cohn PF (1982) Modification of abnormal left ventricular diastolic properties by nifedipine in patients with hypertrophic cardiomyopathy. Circulation 65: 499–507PubMedCrossRefGoogle Scholar
  2. 2.
    Friedel HA, Sorkin EM (1988) Nisoldipine. A preliminary review of its pharmacodynamic and pharmakokinetic properties and therapeutic efficiency in the treatment of angina pectoris, hypertension and related cardiovascular disorders. Drugs 36: 682–731PubMedCrossRefGoogle Scholar
  3. 3.
    Nakaya H, Hattori Y, Nakao Y, Kanno M (1988) Cardiac versus vascular effects of a new dihydropyridine derivative, CV-4093. In vitro comparison with other calcium antagonists. Eur J Pharmacol 146: 35–43PubMedCrossRefGoogle Scholar
  4. 4.
    Lewis BS, Shefer A, Merdier A, Flugelman MY, Hardoff R, Halon DA (1988) Effect of the second-generation calcium channel blocker nisoldipine on left ventricular contractility in cardiac failure. Am Heart J 115: 1238–1244PubMedCrossRefGoogle Scholar
  5. 5.
    Kimball BP, Watson KR, Bui S, Frankel D (1990) Preservation of left ventricular performance with reduced ischemic dysfunction by intravenous nisoldipine. Am J Cardiol 66: 400–405PubMedCrossRefGoogle Scholar
  6. 6.
    Lewis BS (1996) Calcium antagonists in patients with left ventricular dysfunction: Back on the bridge? J Cardiac Failure 2: S259 - S265CrossRefGoogle Scholar
  7. 7.
    Dunselman PHJM, Kuntze CEE, van Bruggen A, Hamer JPM, Scaf AHJ, Wesseling H, Lie KI (1989) Efficacy of felodipine in congestive heart failure. Eur Heart J 10: 354–364PubMedGoogle Scholar
  8. 8.
    Kassis E, Amtorp O (1990) Long-term clinical, haemodynamic, angiographic, and neurohumoral responses to vasodilation with felodipine in patients with chronic congestive heart failure J Cardiovasc Pharmacol 15: 347–352PubMedCrossRefGoogle Scholar
  9. 9.
    Packer M, Nicod P, Khondheria BR, Costello DL, Wasserman AG, Konstam MA, Weiss RJ, Moyer RR, Pinsky DJ, Abittan MH, Souhrada JF (1991) Randomized multicentre, double-blind, placebo-controlled evaluation of amlodipine in patients with mild to moderate heart failure. J Am Coll Cardiol 17:274 ACrossRefGoogle Scholar
  10. 10.
    Godfraind T (1994) Cardioselectivity of calcium antagonists. Cardiovasc Drugs Ther 8: 353–364PubMedCrossRefGoogle Scholar
  11. 11.
    Godfraind T, Salomone S, Dessy C, Verhelst B, Dion R, Schoevaerts JC (1992) Selectivity scale of calcium antagonists in the human cardiovascular system based on in vitro studies. J Cardiovasc Pharmacol 20 (Suppl 5): 34–41Google Scholar
  12. 12.
    Heusch G (1994) Ischemia-selectivity: a new concept of cardioprotection by calcium antagonists. Basic Res Cardiol 89: 2–5PubMedCrossRefGoogle Scholar
  13. 13.
    Knorr AM (1995) Why is nisoldipine a specific agent in ischemic left ventricular dysfunction? Am J Cardiol 75: 36E - 40EPubMedCrossRefGoogle Scholar
  14. 14.
    Aschenberg W, Nienaber C, Spielmann R, Fehr A, Clausen A, Bleifeld W (1987) Acute hemodynamic response of intravenous nisoldipine (Bay k5552) versus nifedipine in patients with ischemic cardiomyopathy. In: Hugenholtz PG, Meyer JD (eds) Nisoldipine 1987. Springer, Berlin Heidelberg New York, pp 263–263Google Scholar
  15. 15.
    Bopp P, Divernois J, Noble J, Gabathuler J (1987) Acute hemodynamic effects of intravenous nisoldipine in patients with left ventricular failure. In: Hugenholtz PG, Meyer JD (eds) Nisoldipine 1987. Springer, Berlin Heidelberg New York, pp 179–182Google Scholar
  16. 16.
    Kiowski W, Erne P, Pfisterer M, Muller J, Buhler FR, Burkart F (1987) Hemodynamic effects of nisoldipine in patients with severe chronic congestive heart failure. In: Hugenholtz PG, Meyer JD (eds) Nisoldipine 1987. Springer, Berlin Heidelberg New York, pp 329–342Google Scholar
  17. 17.
    Lewis BS, Shefer A, Merdler A, Flugelman MY, Hardoff R, Halon DA (1987) Acute effects of intravenous nisoldipine on hemodynamics and left ventricular function in cardiac failure In: Hugenholtz PG, Meyer JD (eds) Nisoldipine 1987. Springer, Berlin Heidelberg New York, pp 315–323CrossRefGoogle Scholar
  18. 18.
    Pouleur H, van Eyll C, Gurne O, Rousseau MF (1992) Analysis of the mechanisms underlying the changes in left ventricular filling dynamics during oral nisoldipine therapy in patients with anterior myocardial infarction. Eur Heart J 13: 952–959PubMedGoogle Scholar
  19. 19.
    Wilcox RG, Hampton JR, Banks DC, Birkhead JS, Brooksby IAB, Burns-Cox CJ, Hayes MJ, Joy MD, Malcolm AD, Mather HG, Rowley JM (1986) Trial of early nifedipine in acute myocardial infarction: the TRENT study. Br Med J 293: 1204–1208CrossRefGoogle Scholar
  20. 20.
    The Israeli Sprint Study Group (1988) Secondary prevention reinfarction Israeli nifedipine trial (SPRINT): a randomised intervention trial of nifedipine in patients with acute myocardial infarction. Eur Heart J 9: 354–364Google Scholar
  21. 21.
    Goldbourt U, Behar S, Reicher-Reiss H, Zion MM, Mandelzweig L, Kaplinsky E, for the SPRINT Study Group (1993) Early administration of nifedipine in suspected acute myocardial infarction. The secondary prevention reinfarction Israel nifedipine trial 2 study. Arch Int Med 153: 345–353CrossRefGoogle Scholar
  22. 22.
    The Multicenter Diltiazem Postinfarction Trial Research Group (1988) The effect of diltiazem on mortality and reinfarction after myocardial infarction. N Engl J Med 319: 385–392CrossRefGoogle Scholar
  23. 23.
    The Danish Study Group on verapamil in myocardial infarction (1990) Effect of verapamil on mortality and major events after acute myocardial infarction (The Danish verapamil infarction trial II–DAVIT II). Am J Cardiol 66: 779–785CrossRefGoogle Scholar
  24. 24.
    The DEFIANT Research Group (1992) Improved diastolic function with the calcium antagonist nisoldipine (coat-core) in patients post-myocardial infarction: results of the DEFIANT study. Eur Heart J 13: 1496–1505Google Scholar
  25. 25.
    The DEFIANT Research Group (1997) Doppler flow and echocardiography in functional cardiac insufficiency: assessment of nisoldipine therapy. Results of the DEFIANT-II study. Eur Heart J 18: 31–40Google Scholar
  26. 26.
    Lewis BS, Emmott SN, Smyllie J, MacNeil AB, Lubsen J, and the DEFIANT Study Group (1993) Left ventricular systolic and diastolic function and exercise capacity 6 to 8 weeks after acute myocardial infarction. Am J Cardiol 72: 149–153PubMedCrossRefGoogle Scholar
  27. 27.
    Brunelli C, Parodi O, Sambuceti G, Corsiglia L, Rosa GM, Giorgetti A, Bezante GP, Nista N, Caponnetto S (1995) Perfusional and metabolic effects of nisoldipine as shown by positron emission tomography after acute myocardial infarction. Am J Cardiol 75: 31E - 35EPubMedCrossRefGoogle Scholar
  28. 28.
    Schulz R, Rose J, Martin C, Brodde O-E, Heusch G (1993) Development of short-term myocardial hibernation. Its limitation by the severity of ischemia and isotropic stimulation. Circulation 88: 684–695PubMedGoogle Scholar
  29. 29.
    Brutsaert DL, Sys SU (1989) Relaxation and diastole of the heart. Phys Rev 69: 1228–1315Google Scholar
  30. 30.
    Marban E (1991) Myocardial stunning and hibernation. The physiology behind the colloquialisms. Circulation 83: 681–688PubMedGoogle Scholar
  31. 31.
    Sheiban I, Tonni S, Benussi P, Marini A, Trevi GP (1993) Left ventricular dysfunction following transient ischemia induced by transluminal coronary angioplasty. Beneficial effects of calcium antagonists against post-ischemic myocardial stunning. Eur Heart J 14 (Suppl A): 14–21PubMedGoogle Scholar
  32. 32.
    Furberg CD, Psaty BM, Meyer JV (1995) Nifedipine: dose related increase in mortality in patients with coronary heart disease. Circulation 92: 1326–1331PubMedGoogle Scholar
  33. 33.
    Psaty BM, Heckbert SR, Koepsell TD, Siscovick DS, Raghunathan TE, Weiss NS, Rosendaal FR, Lemaitre RN, Smith NL, Wahl PW, Wagner EH, Furberg CD (1995) The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA 274: 620–625PubMedCrossRefGoogle Scholar
  34. 34.
    Elkayam U, Roth A, Hsueh W, Weber L, Freidenberger L, Rahimtoola SH (1986) Neurohumoral consequences of vasodilator therapy with hydralazine and nifedipine in severe congestive heart failure. Am Heart J 111: 1130–1138PubMedCrossRefGoogle Scholar
  35. 35.
    Packer M (1990) Calcium channel blockers in chronic heart failure. The risks of “physiologically rational therapy”. Circulation 82: 2254–2257PubMedCrossRefGoogle Scholar
  36. 36.
    Lewis BS (1995) Efficacy and safety of nisoldipine-CC in the management of angina pectoris, systemic hypertension and ischemic ventricular dysfunction. Am J Cardiol 75: 46E - 53EPubMedCrossRefGoogle Scholar
  37. 37.
    Cohn JN, Ziesche S, Smith R, Anand I, Dunkman WB, Loeb H, Cintron G, Boden W, Baruch L, Rochin P, Loss L (1997) Effect of the calcium antagonist felodipine as supplementary vasodilator therapy in patients with chronic heart failure treated with enalapril: V-HeFT III. Vasodilator-Heart Failure Trial (V-HeFT) Study Group. Circulation 96: 856–863PubMedGoogle Scholar
  38. 38.
    Packer M, O’Connor CM, Ghali JK, Pressler ML, Carson PE, Belkin RN, Miller AB, Neuberg GW, Frid D, Wertheimer JH, Cropp AB, De Mets DL (1996) Effect of amlodipine on morbidity and mortality in severe chronic heart failure. Prospective Randomized Amlodipine Survival Evaluation Study Group. N Engl J Med 335: 1107–1114PubMedCrossRefGoogle Scholar
  39. 39.
    Boden WE (1998) INTERCEPT Study. AHA, Dallas, Hotline SessionGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

There are no affiliations available

Personalised recommendations