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November 2, 1994, Vol 272, No. 17 >
ARTICLE | November 2, 1994

Management of Heart Failure: Title and subTitle BreakI. Pharmacologic Treatment FREE

David W. Baker, MD, MPH; Marvin A. Konstam, MD; Michael Bottorff, PharmD; Bertram Pitt, MD
[+] Author Affiliations

The views expressed herein are those of the authors and do not reflect the position of the Agency for Health Care Policy and Research, the US Public Health Service, or the US Department of Health and Human Services.

Reprint requests to New England Medical Center, Box 108, 750 Washington St, Boston, MA 02111 (Dr Konstam).


JAMA. 1994;272(17):1361-1366. doi:10.1001/jama.1994.03520170071039
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Article
References

Objective.  —This review of the pharmacologic treatment of heart failure due to left ventricular systolic dysfunction summarizes the recommendations of the expert panel for the Agency for Health Care Policy and Research Heart Failure Guideline. It provides specific advice to help guide practitioners through clinical decision making.

Data Sources.  —Data were obtained from English-language studies and referenced in MEDLINE or EMBASE between 1966 and 1993. We used the search terms heart failure, congestive; congestive heart failure; heart failure; cardiac failure; and dilated cardiomyopathy in conjunction with terms for the specific treatments. Where data were lacking, we relied on opinions of panel members and peer reviewers.

Study Selection.  —Only large prospective trials were used to estimate treatment efficacy. Smaller trials, case series, and case reports were reviewed for the incidence of adverse effects.

Data Extraction and Synthesis.  —Randomized clinical trials were reviewed for inclusion and exclusion criteria, patient outcomes, adverse effects, and eight categories of study quality using a defined list of study flaws.

Conclusion.  —Angiotensin-converting enzyme (ACE) inhibitors should be given to all patients unless specific contraindications exist. Diuretics should be used judiciously early in treatment to prevent excessive diuresis that could prevent titration of ACE inhibitors to target doses. Digoxin has not been shown to affect the natural history of heart failure and should be reserved for patients who remain symptomatic after treatment with ACE inhibitors and diuretics. Isosorbide dinitrate and hydralazine hydrochloride should be tried in patients who cannot tolerate ACE inhibitors or who have refractory symptoms.(JAMA. 1994;272:1361-1366)

REFERENCES

1 +
SOLVD Investigators.  Effect of enalapril on survival in patients with reduced left-ventricular ejection fractions and congestive heart failure. N Engl J Med . 1991;;325:293-302.
2 +
CONSENSUS Trial Study Group.  Effects of enalapril on mortality in severe congestive heart failure. N Engl J Med . 1987;;316:1429-1435.
3 +
Cohn JN, Archibald DG, Ziesche S, et al.  Effect of vasodilator therapy on mortality in chronic congestive heart failure: results of a Veterans Administration cooperative study. N Engl J Med . 1986;; 314:1547-1552.
4 +
Braunwald E.  ACE inhibitors: a cornerstone of the treatment of heart failure. N Engl J Med . 1991;; 325:351-353.
5 +
Christoph I, Minotti J, Massie BM.  Congestive heart failure: current status of treatment. Prog Cardiol . 1991;;4:3-42.
6 +
Barnett DB, Pouleur H, Francis GS. Congestive Heart Failure: Pathophysiology and Treatment . New York, NY: Marcel Dekker Inc; 1993;.
7 +
Dracup K, Baker D, Dunbar S, et al.  Management of heart failure, II: counseling, education, and lifestyle modifications. JAMA . In press.
8 +
Küpper AJ, Fintelman H, Huige MC, Liem KL, Lustermans FA.  Cross-over comparison of the fixed combination of hydrochlorothiazide and triamterene and the free combination of furosemide and triamterene in the maintenance treatment of congestive heart failure. Eur J Clin Pharmacol . 1986;;30:342-343.
9 +
Whight C, Morgan T, Carney S, Wilson M.  Diuretics, cardiac failure and potassium depletion: a rational approach. Med J Aust . 1974;;2:831-833.
10 +
Brater DC, Day B, Burdette A, Anderson S.  Bumetanide and furosemide in heart failure. Kidney Int . 1984;;26:183-189.
11 +
Vasko MR, Cartwright DB, Knochel JP, Nixon JV, Brater DC.  Furosemide absorption altered in decompensated congestive heart failure. Ann Intern Med . 1985;;102:314-318.
12 +
Edmonds CJ, Jasani B.  Total-body potassium in hypertensive patients during prolonged diuretic therapy. Lancet . 1972;;2:8-12.
13 +
Cohn JN, Johnson G, Ziesche S, et al.  A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med . 1991;;325:303-310.
14 +
Bussmann WD, Storger H, Hadler D, et al.  Long-term treatment of severe chronic heart failure with captopril: a double-blind, randomized, placebo-controlled, long-term study. J Cardiovasc Pharmacol . 1987;;2:50-60.
15 +
The Captopril-Digoxin Multicenter Research Group.  A placebo-controlled trial of captopril in refractory chronic congestive heart failure. J Am Coll Cardiol . 1983;;2:755-763.
16 +
Franciosa JA, Wilen MM, Jordan RA.  Effects of enalapril, a new angiotensin-converting enzyme inhibitor, in a controlled trial in heart failure. J Am Coll Cardiol . 1985;;5:101-107.
17 +
Jennings G, Kiat H, Nelson L, Kelly MJ, Kalff V, Johns J.  Enalapril for severe congestive heart failure: a double-blind study. Med J Aust . 1984;;141: 723-726.
18 +
Kleber FX, Niemoller L, Fischer M, Doering W.  Influence of severity of heart failure on the efficacy of angiotensin-converting enzyme inhibition. Am J Cardiol . 1991;;68:121-126.
19 +
Magnani B, Magelli C.  Captopril in mild heart failure: preliminary observations of a long-term, double-blind, placebo-controlled multicentre trial. Postgrad Med J . 1986;;62:153-158.
20 +
McGrath BP, Arnolda L, Matthews PG, et al.  Controlled trial of enalapril in congestive heart failure. Br Heart J . 1985;;54:405-414.
21 +
Remes J, Nikander P, Rehnberg S, et al.  Enalapril in chronic heart failure: a double-blind placebo-controlled study. Ann Clin Res . 1986;;18:124-128.
22 +
Sharpe D, Murphy J, Coxon R, Hannan SF.  Enalapril in patients with chronic heart failure: a placebo-controlled, randomized, double-blind study. Circulation . 1984;;70:271-278.
23 +
Chalmers JP, West MJ, Cyran J, et al.  Placebo-controlled study of lisinopril in congestive heart failure: a multicentre study. J Cardiovasc Pharmacol . 1987;;9:89-97.
24 +
Lewis GR.  Comparison of lisinopril versus placebo for congestive heart failure. Am J Cardiol . 1989;;63:12-16.
25 +
Riegger GA.  The effects of ACE inhibitors on exercise capacity in the treatment of congestive heart failure. J Cardiovasc Pharmacol . 1990;;15:41-46.
26 +
Riegger GA.  Effects of quinapril on exercise tolerance in patients with mild to moderate heart failure. Eur Heart J . 1991;;12:705-711.
27 +
Cody RJ.  Management of refractory congestive heart failure. Am J Cardiol . 1992;;4:141-149.
28 +
Brogden RN, Todd PA, Sorkin EM.  Captopril: an update of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure. Drugs . 1988;; 36:540-600.
29 +
Cleland JG, Dargie HJ.  Heart failure, renal function, and angiotensin converting enzyme inhibitors. Kidney Int . 1987;;31:220-228.
30 +
Cleland JG, Gillen G, Dargie JH.  The effects of fursemide and angiotensin-converting enzyme inhibitors and their combination on cardiac and renal hemodynamics in heart failure. Eur Heart J . 1988;; 9:132-141.
31 +
Crantock L, Prentice R, Powell L.  Cholestataic jaundice associated with captopril therapy. J Gastroenterol Hepatol . 1991;;6:528-530.
32 +
Denham MJ, Dobbs RJ, Dobbs SM.  Evaluation of the safety of enalapril in the treatment of heart failure in the very old. Eur J Clin Pharmacol . 1988;;35:143-150.
33 +
Frank GJ.  The safety of ACE inhibitors for the treatment of hypertension and congestive heart failure. Cardiology . 1989;;76:56-67.
34 +
Hasford J, Bussmann WD, Delius W, Koepeke W, Lehmann K, Weber E.  First dose hypotension with enalapril and prazosin in congestive heart failure. Int J Cardiol . 1991;;31:287-294.
35 +
Kjekshus J, Swedberg K.  Tolerability of enalapril in congestive heart failure. Am J Cardiol . 1988;; 62:67-72.
36 +
O'Neill CJ, Bowes SG, Sullens CM, et al.  Evaluation of the safety of enalapril in the treatment of heart failure in the very old. Eur J Clin Pharmacol . 1988;;35:143-150.
37 +
Packer M.  Identification of risk factors predisposing to the development of functional renal insufficiency during treatment with converting-enzyme inhibitors in chronic heart failure. Cardiology . 1989;;76:50-55.
38 +
Suki WN.  Renal hemodynamic consequences of angiotensin-converting enzyme inhibition in congestive heart failure. Arch Intern Med . 1989;;149: 669-673.
39 +
Warner NJ, Rush JE, Keegan ME.  Tolerability of enalapril in congestive heart failure. Am J Cardiol . 1989;;63:33-37.
40 +
Packer M, Gheorghiade M, Young JB, et al.  Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting enzyme inhibitors: RADIANCE study. N Engl J Med . 1993;;329:1-7.
41 +
Jaeschke R, Oxman AD, Guyatt GH.  To what extent do congestive heart failure patients in sinus rhythm benefit from digoxin therapy? a systematic overview and meta-analysis. Am J Med . 1990;;88: 279-286.
42 +
DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, 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;;321:476.
43 +
Marcus FI.  Pharmacokinetic interactions between digoxin and other drugs. J Am Coll Cardiol . 1985;;5:82-90.
44 +
Elkayam U.  Tolerance to organic nitrates: evidence, mechanisms, clinical relevance, and strategies for prevention. Ann Intern Med . 1991;;114:667-677.

Figures

Tables

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
SOLVD Investigators.  Effect of enalapril on survival in patients with reduced left-ventricular ejection fractions and congestive heart failure. N Engl J Med . 1991;;325:293-302.
2 +
CONSENSUS Trial Study Group.  Effects of enalapril on mortality in severe congestive heart failure. N Engl J Med . 1987;;316:1429-1435.
3 +
Cohn JN, Archibald DG, Ziesche S, et al.  Effect of vasodilator therapy on mortality in chronic congestive heart failure: results of a Veterans Administration cooperative study. N Engl J Med . 1986;; 314:1547-1552.
4 +
Braunwald E.  ACE inhibitors: a cornerstone of the treatment of heart failure. N Engl J Med . 1991;; 325:351-353.
5 +
Christoph I, Minotti J, Massie BM.  Congestive heart failure: current status of treatment. Prog Cardiol . 1991;;4:3-42.
6 +
Barnett DB, Pouleur H, Francis GS. Congestive Heart Failure: Pathophysiology and Treatment . New York, NY: Marcel Dekker Inc; 1993;.
7 +
Dracup K, Baker D, Dunbar S, et al.  Management of heart failure, II: counseling, education, and lifestyle modifications. JAMA . In press.
8 +
Küpper AJ, Fintelman H, Huige MC, Liem KL, Lustermans FA.  Cross-over comparison of the fixed combination of hydrochlorothiazide and triamterene and the free combination of furosemide and triamterene in the maintenance treatment of congestive heart failure. Eur J Clin Pharmacol . 1986;;30:342-343.
9 +
Whight C, Morgan T, Carney S, Wilson M.  Diuretics, cardiac failure and potassium depletion: a rational approach. Med J Aust . 1974;;2:831-833.
10 +
Brater DC, Day B, Burdette A, Anderson S.  Bumetanide and furosemide in heart failure. Kidney Int . 1984;;26:183-189.
11 +
Vasko MR, Cartwright DB, Knochel JP, Nixon JV, Brater DC.  Furosemide absorption altered in decompensated congestive heart failure. Ann Intern Med . 1985;;102:314-318.
12 +
Edmonds CJ, Jasani B.  Total-body potassium in hypertensive patients during prolonged diuretic therapy. Lancet . 1972;;2:8-12.
13 +
Cohn JN, Johnson G, Ziesche S, et al.  A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med . 1991;;325:303-310.
14 +
Bussmann WD, Storger H, Hadler D, et al.  Long-term treatment of severe chronic heart failure with captopril: a double-blind, randomized, placebo-controlled, long-term study. J Cardiovasc Pharmacol . 1987;;2:50-60.
15 +
The Captopril-Digoxin Multicenter Research Group.  A placebo-controlled trial of captopril in refractory chronic congestive heart failure. J Am Coll Cardiol . 1983;;2:755-763.
16 +
Franciosa JA, Wilen MM, Jordan RA.  Effects of enalapril, a new angiotensin-converting enzyme inhibitor, in a controlled trial in heart failure. J Am Coll Cardiol . 1985;;5:101-107.
17 +
Jennings G, Kiat H, Nelson L, Kelly MJ, Kalff V, Johns J.  Enalapril for severe congestive heart failure: a double-blind study. Med J Aust . 1984;;141: 723-726.
18 +
Kleber FX, Niemoller L, Fischer M, Doering W.  Influence of severity of heart failure on the efficacy of angiotensin-converting enzyme inhibition. Am J Cardiol . 1991;;68:121-126.
19 +
Magnani B, Magelli C.  Captopril in mild heart failure: preliminary observations of a long-term, double-blind, placebo-controlled multicentre trial. Postgrad Med J . 1986;;62:153-158.
20 +
McGrath BP, Arnolda L, Matthews PG, et al.  Controlled trial of enalapril in congestive heart failure. Br Heart J . 1985;;54:405-414.
21 +
Remes J, Nikander P, Rehnberg S, et al.  Enalapril in chronic heart failure: a double-blind placebo-controlled study. Ann Clin Res . 1986;;18:124-128.
22 +
Sharpe D, Murphy J, Coxon R, Hannan SF.  Enalapril in patients with chronic heart failure: a placebo-controlled, randomized, double-blind study. Circulation . 1984;;70:271-278.
23 +
Chalmers JP, West MJ, Cyran J, et al.  Placebo-controlled study of lisinopril in congestive heart failure: a multicentre study. J Cardiovasc Pharmacol . 1987;;9:89-97.
24 +
Lewis GR.  Comparison of lisinopril versus placebo for congestive heart failure. Am J Cardiol . 1989;;63:12-16.
25 +
Riegger GA.  The effects of ACE inhibitors on exercise capacity in the treatment of congestive heart failure. J Cardiovasc Pharmacol . 1990;;15:41-46.
26 +
Riegger GA.  Effects of quinapril on exercise tolerance in patients with mild to moderate heart failure. Eur Heart J . 1991;;12:705-711.
27 +
Cody RJ.  Management of refractory congestive heart failure. Am J Cardiol . 1992;;4:141-149.
28 +
Brogden RN, Todd PA, Sorkin EM.  Captopril: an update of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure. Drugs . 1988;; 36:540-600.
29 +
Cleland JG, Dargie HJ.  Heart failure, renal function, and angiotensin converting enzyme inhibitors. Kidney Int . 1987;;31:220-228.
30 +
Cleland JG, Gillen G, Dargie JH.  The effects of fursemide and angiotensin-converting enzyme inhibitors and their combination on cardiac and renal hemodynamics in heart failure. Eur Heart J . 1988;; 9:132-141.
31 +
Crantock L, Prentice R, Powell L.  Cholestataic jaundice associated with captopril therapy. J Gastroenterol Hepatol . 1991;;6:528-530.
32 +
Denham MJ, Dobbs RJ, Dobbs SM.  Evaluation of the safety of enalapril in the treatment of heart failure in the very old. Eur J Clin Pharmacol . 1988;;35:143-150.
33 +
Frank GJ.  The safety of ACE inhibitors for the treatment of hypertension and congestive heart failure. Cardiology . 1989;;76:56-67.
34 +
Hasford J, Bussmann WD, Delius W, Koepeke W, Lehmann K, Weber E.  First dose hypotension with enalapril and prazosin in congestive heart failure. Int J Cardiol . 1991;;31:287-294.
35 +
Kjekshus J, Swedberg K.  Tolerability of enalapril in congestive heart failure. Am J Cardiol . 1988;; 62:67-72.
36 +
O'Neill CJ, Bowes SG, Sullens CM, et al.  Evaluation of the safety of enalapril in the treatment of heart failure in the very old. Eur J Clin Pharmacol . 1988;;35:143-150.
37 +
Packer M.  Identification of risk factors predisposing to the development of functional renal insufficiency during treatment with converting-enzyme inhibitors in chronic heart failure. Cardiology . 1989;;76:50-55.
38 +
Suki WN.  Renal hemodynamic consequences of angiotensin-converting enzyme inhibition in congestive heart failure. Arch Intern Med . 1989;;149: 669-673.
39 +
Warner NJ, Rush JE, Keegan ME.  Tolerability of enalapril in congestive heart failure. Am J Cardiol . 1989;;63:33-37.
40 +
Packer M, Gheorghiade M, Young JB, et al.  Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting enzyme inhibitors: RADIANCE study. N Engl J Med . 1993;;329:1-7.
41 +
Jaeschke R, Oxman AD, Guyatt GH.  To what extent do congestive heart failure patients in sinus rhythm benefit from digoxin therapy? a systematic overview and meta-analysis. Am J Med . 1990;;88: 279-286.
42 +
DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, 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;;321:476.
43 +
Marcus FI.  Pharmacokinetic interactions between digoxin and other drugs. J Am Coll Cardiol . 1985;;5:82-90.
44 +
Elkayam U.  Tolerance to organic nitrates: evidence, mechanisms, clinical relevance, and strategies for prevention. Ann Intern Med . 1991;;114:667-677.

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