Abstract
OBJECTIVE--Neurohormonal activation has major impact on the pathophysiology of congestive heart failure. The Munich Mild Heart Failure Trial was designed to test the hypothesis that interference with the renin-angiotensin system by angiotensin converting enzyme inhibition favourably influences the natural history of heart failure. DESIGN AND PATIENTS--170 patients, median New York Heart Association (NYHA) class II, were randomised to double blind treatment with 25 mg captopril twice a day or placebo in addition to standard treatment for a median observation period of 2.7 years. MAIN OUTCOME MEASURES--Progression of heart failure to NYHA class IV on an optimally adjusted standard treatment, death due to progressive heart failure, and sudden death. RESULTS--Heart failure progressed to class IV in nine patients (10.8%) treated with captopril and in 23 patients (26.4%) treated with placebo (p = 0.01). The mean survival time until this end point was 223 days longer in the captopril group (Kaplan-Meier life table analysis; p = 0.02). Also, progressive deterioration to severe heart failure was a powerful predictor of total mortality and death from heart failure; 80% of deaths due to progressive heart failure occurred after this end point. There were fewer deaths caused by progressive heart failure in the captopril group than in the placebo group (4 v 11; p = 0.10) but similar numbers of sudden deaths (11 v 10). Progressive heart failure was the cause of death in 18.2% of all deaths in the captopril group and 50% in the placebo group. Total heart failure events (the end point on which power calculation was based) were also more common in the placebo group (19 v 32 events) but not significantly so. Total mortality was similar to both groups (22 of 83 v 22 of 87). CONCLUSIONS--Angiotensin converting enzyme inhibition in conjunction with standard therapy early in the course of congestive heart failure slowed the progress of heart failure and thus favourably altered the natural history of the disease.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bayliss J., Norell M., Canepa-Anson R., Sutton G., Poole-Wilson P. Untreated heart failure: clinical and neuroendocrine effects of introducing diuretics. Br Heart J. 1987 Jan;57(1):17–22. doi: 10.1136/hrt.57.1.17. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bertel O., Conen D., Schwarz U., Besch W., Dubach U. C. Verbessert die engmaschige Kontrolle und Therapie-Anpassung die Prognose bei schwer herzinsuffizienten Patienten? Schweiz Med Wochenschr. 1985 Dec 14;115(50):1820–1823. [PubMed] [Google Scholar]
- Chatterjee K., Parmley W. W., Cohn J. N., Levine T. B., Awan N. A., Mason D. T., Faxon D. P., Creager M., Gavras H. P., Fouad F. M. A cooperative multicenter study of captopril in congestive heart failure: hemodynamic effects and long-term response. Am Heart J. 1985 Aug;110(2):439–447. doi: 10.1016/0002-8703(85)90167-x. [DOI] [PubMed] [Google Scholar]
- Cleland J. G., Dargie H. J., Ball S. G., Gillen G., Hodsman G. P., Morton J. J., East B. W., Robertson I., Ford I., Robertson J. I. Effects of enalapril in heart failure: a double blind study of effects on exercise performance, renal function, hormones, and metabolic state. Br Heart J. 1985 Sep;54(3):305–312. doi: 10.1136/hrt.54.3.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cleland J. G., Dargie H. J., Hodsman G. P., Ball S. G., Robertson J. I., Morton J. J., East B. W., Robertson I., Murray G. D., Gillen G. Captopril in heart failure. A double blind controlled trial. Br Heart J. 1984 Nov;52(5):530–535. doi: 10.1136/hrt.52.5.530. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cohn J. N., Archibald D. G., Ziesche S., Franciosa J. A., Harston W. E., Tristani F. E., Dunkman W. B., Jacobs W., Francis G. S., Flohr K. H. Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med. 1986 Jun 12;314(24):1547–1552. doi: 10.1056/NEJM198606123142404. [DOI] [PubMed] [Google Scholar]
- DiBianco R., Shabetai R., Kostuk W., Moran J., Schlant R. C., Wright R. A comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. N Engl J Med. 1989 Mar 16;320(11):677–683. doi: 10.1056/NEJM198903163201101. [DOI] [PubMed] [Google Scholar]
- Gottlieb S. S., Kukin M. L., Ahern D., Packer M. Prognostic importance of atrial natriuretic peptide in patients with chronic heart failure. J Am Coll Cardiol. 1989 Jun;13(7):1534–1539. doi: 10.1016/0735-1097(89)90344-6. [DOI] [PubMed] [Google Scholar]
- Gradman A., Deedwania P., Cody R., Massie B., Packer M., Pitt B., Goldstein S. Predictors of total mortality and sudden death in mild to moderate heart failure. Captopril-Digoxin Study Group. J Am Coll Cardiol. 1989 Sep;14(3):564–572. doi: 10.1016/0735-1097(89)90093-4. [DOI] [PubMed] [Google Scholar]
- Hammermeister K. E., DeRouen T. A., Dodge H. T. Variables predictive of survival in patients with coronary disease. Selection by univariate and multivariate analyses from the clinical, electrocardiographic, exercise, arteriographic, and quantitative angiographic evaluations. Circulation. 1979 Mar;59(3):421–430. doi: 10.1161/01.cir.59.3.421. [DOI] [PubMed] [Google Scholar]
- Hinkle L. E., Jr, Thaler H. T. Clinical classification of cardiac deaths. Circulation. 1982 Mar;65(3):457–464. doi: 10.1161/01.cir.65.3.457. [DOI] [PubMed] [Google Scholar]
- Jeremy R. W., Allman K. C., Bautovitch G., Harris P. J. Patterns of left ventricular dilation during the six months after myocardial infarction. J Am Coll Cardiol. 1989 Feb;13(2):304–310. doi: 10.1016/0735-1097(89)90503-2. [DOI] [PubMed] [Google Scholar]
- Kleber F. X. ACE inhibitors after myocardial infarction. Lancet. 1990 Feb 3;335(8684):295–295. doi: 10.1016/0140-6736(90)90117-n. [DOI] [PubMed] [Google Scholar]
- Kleber F. X., Einwang H. P., Kronski D., Ohly A., Osterkorn K., Doering W. Progrediente linksventrikuläre Dilatation nach Vorderwandinfarkt als Determinante für die Entwicklung einer Herzinsuffizienz. Z Kardiol. 1990 Jan;79(1):1–7. [PubMed] [Google Scholar]
- Kramer B. L., Massie B. M., Topic N. Controlled trial of captopril in chronic heart failure: a rest and exercise hemodynamic study. Circulation. 1983 Apr;67(4):807–816. doi: 10.1161/01.cir.67.4.807. [DOI] [PubMed] [Google Scholar]
- Lee W. H., Packer M. Prognostic importance of serum sodium concentration and its modification by converting-enzyme inhibition in patients with severe chronic heart failure. Circulation. 1986 Feb;73(2):257–267. doi: 10.1161/01.cir.73.2.257. [DOI] [PubMed] [Google Scholar]
- McKee P. A., Castelli W. P., McNamara P. M., Kannel W. B. The natural history of congestive heart failure: the Framingham study. N Engl J Med. 1971 Dec 23;285(26):1441–1446. doi: 10.1056/NEJM197112232852601. [DOI] [PubMed] [Google Scholar]
- Miller M. A proposed solution to the present organ donation crisis based on a hard look at the past. Circulation. 1987 Jan;75(1):20–28. doi: 10.1161/01.cir.75.1.20. [DOI] [PubMed] [Google Scholar]
- Newman T. J., Maskin C. S., Dennick L. G., Meyer J. H., Hallows B. G., Cooper W. H. Effects of captopril on survival in patients with heart failure. Am J Med. 1988 Mar 11;84(3A):140–144. doi: 10.1016/0002-9343(88)90221-5. [DOI] [PubMed] [Google Scholar]
- Packer M., Medina N., Yushak M. Correction of dilutional hyponatremia in severe chronic heart failure by converting-enzyme inhibition. Ann Intern Med. 1984 Jun;100(6):782–789. doi: 10.7326/0003-4819-100-6-782. [DOI] [PubMed] [Google Scholar]
- Pfeffer M. A., Lamas G. A., Vaughan D. E., Parisi A. F., Braunwald E. Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. N Engl J Med. 1988 Jul 14;319(2):80–86. doi: 10.1056/NEJM198807143190204. [DOI] [PubMed] [Google Scholar]
- Pfeffer M. A., Pfeffer J. M., Steinberg C., Finn P. Survival after an experimental myocardial infarction: beneficial effects of long-term therapy with captopril. Circulation. 1985 Aug;72(2):406–412. doi: 10.1161/01.cir.72.2.406. [DOI] [PubMed] [Google Scholar]
- Rockman H. A., Juneau C., Chatterjee K., Rouleau J. L. Long-term predictors of sudden and low output death in chronic congestive heart failure secondary to coronary artery disease. Am J Cardiol. 1989 Dec 1;64(19):1344–1348. doi: 10.1016/0002-9149(89)90579-1. [DOI] [PubMed] [Google Scholar]
- Sharpe D. N., Murphy J., Coxon R., Hannan S. F. Enalapril in patients with chronic heart failure: a placebo-controlled, randomized, double-blind study. Circulation. 1984 Aug;70(2):271–278. doi: 10.1161/01.cir.70.2.271. [DOI] [PubMed] [Google Scholar]
- Sharpe N., Murphy J., Smith H., Hannan S. Treatment of patients with symptomless left ventricular dysfunction after myocardial infarction. Lancet. 1988 Feb 6;1(8580):255–259. doi: 10.1016/s0140-6736(88)90347-9. [DOI] [PubMed] [Google Scholar]
- Sweet C. S., Emmert S. E., Stabilito I. I., Ribeiro L. G. Increased survival in rats with congestive heart failure treated with enalapril. J Cardiovasc Pharmacol. 1987 Dec;10(6):636–642. doi: 10.1097/00005344-198712000-00005. [DOI] [PubMed] [Google Scholar]
- Webster M. W., Fitzpatrick M. A., Nicholls M. G., Ikram H., Wells J. E. Effect of enalapril on ventricular arrhythmias in congestive heart failure. Am J Cardiol. 1985 Sep 15;56(8):566–569. doi: 10.1016/0002-9149(85)91186-5. [DOI] [PubMed] [Google Scholar]
- White H. D., Norris R. M., Brown M. A., Brandt P. W., Whitlock R. M., Wild C. J. Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation. 1987 Jul;76(1):44–51. doi: 10.1161/01.cir.76.1.44. [DOI] [PubMed] [Google Scholar]
- Wilson J. R., Schwartz J. S., Sutton M. S., Ferraro N., Horowitz L. N., Reichek N., Josephson M. E. Prognosis in severe heart failure: relation to hemodynamic measurements and ventricular ectopic activity. J Am Coll Cardiol. 1983 Sep;2(3):403–410. doi: 10.1016/s0735-1097(83)80265-4. [DOI] [PubMed] [Google Scholar]
- de Langen C. D., de Graeff P. A., van Gilst W. H., Bel K. J., Kingma J. H., Wesseling H. Effects of angiotensin II and captopril on inducible sustained ventricular tachycardia two weeks after myocardial infarction in the pig. J Cardiovasc Pharmacol. 1989 Feb;13(2):186–191. doi: 10.1097/00005344-198902000-00002. [DOI] [PubMed] [Google Scholar]
- van Gilst W. H., de Graeff P. A., Wesseling H., de Langen C. D. Reduction of reperfusion arrhythmias in the ischemic isolated rat heart by angiotensin converting enzyme inhibitors: a comparison of captopril, enalapril, and HOE 498. J Cardiovasc Pharmacol. 1986 Jul-Aug;8(4):722–728. [PubMed] [Google Scholar]