A placebo-controlled trial of captopril in refractory chronic congestive heart failure. Captopril Multicenter Research Group

Ninety-two patients with heart failure refractory to digitalis and diuretic therapy had captopril (n = 50) or placebo (n = 42) added to their therapeutic regimen in a randomized, double-blind trial. During a 2 week dosage titration period, one captopril-treated patient died of an intracerebral hemorrhage. Over the remaining 10 week evaluation period, 1 captopril-treated patient (2%) was excluded from the study because of treatment failure as compared with 12 discontinuations (4 deaths and 8 failures [29%]) among the placebo group (p less than 0.001). Eighty percent of patients in the captopril group exhibited some degree of clinical improvement, whereas only 27% in the placebo group did so (p less than 0.001). The therapeutic advantage of captopril over placebo was evidenced by a mean improvement of 0.52 (2.8 +/- 0.1 to 2.3 +/- 0.1) in the New York Heart Association functional class value as compared with 0.03 (2.9 +/- 0.1 to 2.8 +/- 0.1) with placebo (p less than 0.0001). There was a 24% mean increase in exercise tolerance with captopril (495 +/- 22 to 614 +/- 27 seconds) as compared with 0.4% with placebo (480 +/- 28 to 483 +/- 43 seconds) (p less than 0.01); the captopril group had an increase in the ejection fraction from a mean baseline value of 0.19 +/- 0.02 to 0.22 +2- 0.02 as compared with 0.19 +/- 0.02 to 0.18 +/- 0.002 (p less than 0.05) in the placebo group. A cohort analysis revealed that improvement in exercise tolerance with captopril was gradual and progressive throughout the 12 weeks. Improvement in specific symptoms of heart failure, that is, dyspnea, fatigue and orthopnea, and the reduction of edema also were greater in the captopril-treated patients (p less than 0.05 to p less than 0.001). Captopril therapy was well tolerated, although symptomatic hypotension after the first dose caused withdrawal of three patients (3%) from the study. It was concluded that captopril is an effective adjunctive treatment to digitalis and diuretic drugs for patients with refractory heart failure.

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				S. Puri, B. L. Baker, D. P. Dutka, C. M. Oakley, J. M. B. Hughes, and J. G. F. Cleland Reduced Alveolar–Capillary Membrane Diffusing Capacity in Chronic Heart Failure : Its Pathophysiological Relevance and Relationship to Exercise Performance Circulation, June 1, 1995; 91(11): 2769 - 2774. [Abstract] [Full Text]

				R. Garg, S. Yusuf, the Collaborative Group on ACE Inhibitor Trials, W. D. Bussmann, P. Sleight, A. Uprichard, B. Massie, B. McGrath, B. Nilsson, B. Pitt, et al. Overview of Randomized Trials of Angiotensin-Converting Enzyme Inhibitors on Mortality and Morbidity in Patients With Heart Failure JAMA, May 10, 1995; 273(18): 1450 - 1456. [Abstract] [PDF]

				I. Crozier, H. Ikram, N. Awan, J. Cleland, N. Stephen, K. Dickstein, M. Frey, J. Young, G. Klinger, L. Makris, et al. Losartan in Heart Failure : Hemodynamic Effects and Tolerability Circulation, February 1, 1995; 91(3): 691 - 697. [Abstract] [Full Text]

				D. W. Baker, M. A. Konstam, M. Bottorff, and B. Pitt Management of Heart Failure: I. Pharmacologic Treatment JAMA, November 2, 1994; 272(17): 1361 - 1366. [Abstract] [PDF]

				R. J. Cody Comparing Angiotensin-Converting Enzyme Inhibitor Trial Results in Patients With Acute Myocardial Infarction Arch Intern Med, September 26, 1994; 154(18): 2029 - 2036. [Abstract] [PDF]

				V.S. Chekanov, A.A. Krakovsky, N.S. Bushlenko, L.G. Riabinina, D.B. Andreev, K.V. Shatalov, I.A. Dubrovsky, V.V. Pekarsky, Sh. D. Akhmedov, N. Trehan, et al. Cardiomyoplasty: Review of Early and Late Results Vascular and Endovascular Surgery, September 1, 1994; 28(7): 481 - 488. [Abstract] [PDF]

				M. Packer, M. Gheorghiade, J. B. Young, P. J. Costantini, K. F. Adams, R. J. Cody, L. K. Smith, L. Van Voorhees, L. A. Gourley, M. K. Jolly, et al. Withdrawal of Digoxin from Patients with Chronic Heart Failure Treated with Angiotensin-Converting-Enzyme Inhibitors N. Engl. J. Med., July 1, 1993; 329(1): 1 - 7. [Abstract] [Full Text]

				D. L. Groden Vasodilator Therapy for Congestive Heart Failure: Lessons From Mortality Trials Arch Intern Med, February 22, 1993; 153(4): 445 - 454. [Abstract] [PDF]

				A. M. Feldman Can We Alter Survival in Patients With Congestive Heart Failure? JAMA, April 8, 1992; 267(14): 1956 - 1961. [Abstract] [PDF]

				J. R. Oster and B. J. Materson Renal and Electrolyte Complications of Congestive Heart Failure and Effects of Therapy With Angiotensin-Converting Enzyme Inhibitors Arch Intern Med, April 1, 1992; 152(4): 704 - 710. [Abstract] [PDF]

				J. Myers and V. F. Froelicher Hemodynamic Determinants of Exercise Capacity in Chronic Heart Failure Ann Intern Med, September 1, 1991; 115(5): 377 - 386. [Abstract] [PDF]

				D. L. Kulick and S. H. Rahimtoola Current Role of Digitalis Therapy in Patients With Congestive Heart Failure JAMA, June 12, 1991; 265(22): 2995 - 2997. [Abstract] [PDF]

				P. C. Deedwania Angiotensin-Converting Enzyme Inhibitors in Congestive Heart Failure Arch Intern Med, September 1, 1990; 150(9): 1798 - 1805. [Abstract] [PDF]

				M. A. Munger, S. F. Gardner, and R. C. Jarvis Endocrinologic Warfare: The Role of Angiotensin-Converting Enzyme Inhibitors in Congestive Heart Failure Journal of Pharmacy Practice, January 1, 1990; 3(5): 318 - 331. [Abstract] [PDF]

				R. Jaeschke and G. H. Guyatt Medical Therapy for Chronic Congestive Heart Failure Ann Intern Med, May 15, 1989; 110(10): 758 - 760. [Abstract] [PDF]

				W. N. Suki Renal Hemodynamic Consequences of Angiotensin-Converting Enzyme Inhibition in Congestive Heart Failure Arch Intern Med, March 1, 1989; 149(3): 669 - 673. [Abstract] [PDF]

				M. Packer Clinical Trials in Congestive Heart Failure: Why Do Studies Report Conflicting Results? Ann Intern Med, July 1, 1988; 109(1): 3 - 5. [Abstract] [PDF]

				P. R. Marantz, M. H. Alderman, and J. N. Tobin Diagnostic Heterogeneity in Clinical Trials for Congestive Heart Failure Ann Intern Med, July 1, 1988; 109(1): 55 - 61. [Abstract] [PDF]

				C. D. Mulrow, J. P. Mulrow, W. D. Linn, C. Aguilar, and G. Ramirez Relative Efficacy of Vasodilator Therapy in Chronic Congestive Heart Failure: Implications of Randomized Trials JAMA, June 17, 1988; 259(23): 3422 - 3426. [Abstract] [PDF]

				The Captopril-Digoxin Multicenter Research Group, J. Cohn, M. Hawkins, H. Levine, J. Naughton, E. Rapaport, S. Goldstein, B. Pitt, S. Goldstein, R. Cody, et al. Comparative Effects of Therapy With Captopril and Digoxin in Patients With Mild to Moderate Heart Failure JAMA, January 22, 1988; 259(4): 539 - 544. [Abstract] [PDF]

				T. D. Giles, M. G. Thomas, A. C. Quiroz, J. C. Rice, W. Plauche, and G. E. Sander Acute and Short-Term Effects of Clonidine in Heart Failure Angiology, July 1, 1987; 38(7): 537 - 548. [Abstract] [PDF]

				M. PACKER, W. H. LEE, N. MEDINA, M. YUSHAK, and P. D. KESSLER Functional Renal Insufficiency During Long-Term Therapy with Captopril and Enalapril in Severe Chronic Heart Failure Ann Intern Med, March 1, 1987; 106(3): 346 - 354. [Abstract] [PDF]

				M. PACKER, W. H. LEE, N. MEDINA, and M. YUSHAK Influence of Renal Function on the Hemodynamic and Clinical Responses to Long-Term Captopril Therapy in Severe Chronic Heart Failure Ann Intern Med, February 1, 1986; 104(2): 147 - 154. [Abstract] [PDF]

				J. Abrams Vasodilator Therapy for Chronic Congestive Heart Failure JAMA, December 6, 1985; 254(21): 3070 - 3074. [Abstract] [PDF]

				G. S. FRANCIS, S. R. GOLDSMITH, T. B. LEVINE, M. T. OLIVARI, and J. N. COHN The Neurohumoral Axis in Congestive Heart Failure Ann Intern Med, September 1, 1984; 101(3): 370 - 377. [Abstract] [PDF]