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May 10, 1995, Vol 273, No. 18 >
ARTICLE | May 10, 1995

Overview of Randomized Trials of Angiotensin-Converting Enzyme Inhibitors on Mortality and Morbidity in Patients With Heart Failure FREE

Rekha Garg, MD, MS; Salim Yusuf, MBBS, FRCP, DPhil; W. D. Bussmann, MD; Peter Sleight, MD; Andrew Uprichard, MD; Barry Massie, MD; Barry McGrath, MD; Berit Nilsson, PhD; Bertram Pitt, MD; Bruno Magnani, MD; Carol Maskin, MD; Ettore Ambrosioni, MD; Ewa Rucinska, MD; Franz X. Kleber, MD; Gary Jennings, MD; Gianni Tognoni, MD; Helmut Drexler, MD; John G. F. Cleland, MD; Joseph A. Franciosa, MD; Jouko Remes, MD; Karl Swedberg, MD; Karl Swedberg, MD; Kenneth Dickstein, MD; Lothar Maass, MD; Marc Pfeffer, MD; Mark A. Creager, MD; Maryann Gordon, MD; Michael Joy, MD; Norman Sharpe, MD; Peter Sleight, MD; Pierre Desche, MD; Robin McGarry, MD; Rory Collins, MD; Steven G. Chrysant, MD; Vincenzo Cicchetti, MD; W. D. Bussmann, MD
[+] Author Affiliations

Dr Yusuf has received monetary compensation for speaking engagements from several pharmaceutical companies, including some that manufacture ACE inhibitors.

A complete list of the Collaborative Group on ACE Inhibitors is provided at the end of this article.

Reprint requests to the Clinical Trials Branch, National Heart, Lung, and Blood Institute, Federal Bldg, Room 5C10, Bethesda, MD 20892 (Dr Garg).


JAMA. 1995;273(18):1450-1456. doi:10.1001/jama.1995.03520420066040
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Article
References

Objective.  —To evaluate the effect of angiotensin-converting enzyme (ACE) inhibitors on mortality and morbidity in patients with symptomatic congestive heart failure.

Data Sources and Study Selection.  —Data were obtained for all completed, published or unpublished, randomized, placebo-controlled trials of ACE inhibitors that were at least 8 weeks in duration and had determined total mortality by intention to treat, regardless of sample size. Trials were identified based on literature review and correspondence with investigators and pharmaceutical firms.

Data Extraction.  —Using standard tables, data were extracted by one author and confirmed where necessary by the other author or the principal investigator of the trial. Unpublished data were obtained by direct correspondence with the principal investigator of each study or pharmaceutical firm.

Data Synthesis.  —The data for each outcome were combined using the Yusuf-Peto adaptation of the Mantel-Haenszel method. Overall, there was a statistically significant reduction in total mortality (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.67 to 0.88; P<.001) and in the combined endpoint of mortality or hospitalization for congestive heart failure (OR, 0.65; 95% CI, 0.57 to 0.74; P<.001). Similar benefits were observed with several different ACE inhibitors, although the data were largely based on enalapril maleate, captopril, ramipril, quinapril hydrochloride, and lisinopril. Reductions for total mortality and the combined endpoint were similar for various subgroups examined (age, sex, etiology, and New York Heart Association class). However, patients with the lowest ejection fraction appeared to have the greatest benefit. The greatest effect was seen during the first 3 months, but additional benefit was observed during further treatment. The reduction in mortality was primarily due to fewer deaths from progressive heart failure (OR, 0.69; 95% CI, 0.58 to 0.83); point estimates for effects on sudden or presumed arrhythmic deaths (OR, 0.91; 95% CI, 0.73 to 1.12) and fatal myocardial infarction (OR, 0.82; 95% CI, 0.60 to 1.11) were less than 1 but were not significant.

Conclusions.  —Total mortality and hospitalization for congestive heart failure are significantly reduced by ACE inhibitors with consistent effects in a broad range of patients.(JAMA. 1995;273:1450-1456)

REFERENCES

1 +
References 1,2,8,11, 13-15,18-22, 24, 25, 28-30, 32-39.
2 +
References 1,2, 10-12, 14, 15, 22, 31, 32, 35, 39.
3 +
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.
4 +
The CONSENSUS Trial Study Group.  Effects of enalapril on mortality in severe congestive heart failure. N Engl J Med . 1987;;316:1429-1435.
5 +
Yusuf S, Peto R, Lewis J, Sleight P.  Beta-blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis . 1985;;17:335-371.
6 +
Early Breast Cancer Trialists' Collaborative Group.  Effect of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer. N Engl J Med . 1988;;319:1681-1692.
7 +
Held PH, Teo KK, Yusuf S.  Effects of beta-blockade, calcium channel blockers, and nitrates in acute myocardial infarction and unstable angina pectoris.  In: Topol EJ, ed. Textbook of Interventional Cardiology . Philadelphia, Pa: WB Saunders Co; 1991;:49-65.
8 +
DerSimonian R, Laird N.  Meta-analysis in clinical trials. Control Clin Trials . 1986;;7:177-188.
9 +
Mantel N, Haenszel W.  Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst . 1959;;22:719-748.
10 +
Colfer HT, Ribner HS, Gradman A, Hughes V, Kapoor A, Laideau JC, for the Benazepril Heart Failure Study Group.  Effects of once-daily benazepril therapy on exercise tolerance and manifestations of chronic congestive heart failure. Am J Cardiol . 1992;;70:354-358.
11 +
McGarry R. Randomized, Double Blind, Multicenter Study Comparing Benazepril to Digoxin and to Placebo as Add On Therapy to Diuretic in Patients With CHF, NYHA Class II-III During a 12-Week Treatment Period, GHBA-194 . Summit, NJ: Ciba-Geigy Pharmaceuticals; September 1991;. Unpublished report.
12 +
Magnani B, Magelli C, for the Multicenter Research Groups on Mild Heart Failure.  Captopril in mild heart failure: preliminary observations of a long-term double-blind, placebo-controlled multi centre trial. Postgrad Med J . 1986;;62( (suppl I) ):153-158.
13 +
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;;9( (suppl 2) ):S50-S60.
14 +
Captopril-Digoxin Multicenter Research Group.  Comparative effects of therapy with captopril and digoxin in patients with mild to moderate heart failure. JAMA . 1988;;259:539-544.
15 +
Newman TJ, Maskin CS, Dennick LG, Meyer JH, Hallows BG, Cooper WH.  Effects of captopril on survival in patients with heart failure. Am J Med . 1988;;84( (suppl 3A) ):140-144.
16 +
Barabino A, Galbariggi G, Pizzorni C, Lotti G.  Comparative effects of long-term therapy with captopril and ibopamine in chronic congestive heart failure in old patients. Cardiology . 1991;;78:289-296.
17 +
Kleber FX, Niemoller L, Doering W.  Impact of converting enzyme inhibition on progression of chronic heart failure: results of the Munich mild heart failure trial. Br Heart J . 1992;;67:289-296.
18 +
Niitani H, Hisakazu Y, Kawai C, et al.  Clinical study of captopril (CS-522 CHF) on chronic heart failure: multicenter double blind study in comparison with placebo [in Japanese]. Rinshioyaku . 1992;; 8:1273-1291.
19 +
Magnani B, Rizzon R. SCIC—Sopravivenza con Captopril nell' Insufficienza Cardiaca: Protocol . Bologna, Italy: SCIC—Sopravivenza con Captopril nell' Insufficienza Cardiaca; 1990;.
20 +
Drexler H, Banhardt BS, Meinertz T, Wollschlager H, Lehmann M, Just H.  Contrasting peripheral short-term and long-term effects of converting enzyme inhibition in patients with congestive heart failure: a double blind, placebo controlled trial. Circulation . 1989;;79:491-502.
21 +
Cleland JGF, Dargie HJ, Ball SG, et al.  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;;54: 305-311.
22 +
Rucinska EJ. A Double Blind Placebo Controlled Study to Evaluate the Effects of Enalapril in Patients With Chronic Heart Failure . West Point, Pa: Merck Sharpe & Dohme Research Laboratories; September 1991;. Unpublished report.
23 +
Enalapril CHF Investigators.  Long-term effects of enalapril in patients with congestive heart failure: a multicenter, placebo-controlled trial. Heart Failure . 1987;;3:102-107.
24 +
Dickstein K, Barvik S, Aarsland T.  Effect of long-term enalapril therapy on cardiopulmonary exercise performance in men with mild heart failure and previous myocardial infarction. J Am Coll Cardiol . 1991;;18:596-602.
25 +
Rucinska EJ. Enalapril vs Placebo in Previously Untreated Patients With CHF . West Point, Pa: Merck Sharpe & Dohme Research Laboratories; September 1991;. Unpublished report.
26 +
Zwehl W, Rucinska E, for Lisinopril Chronic Heart Failure Investigators.  Long-term effects of lisinopril in patients with chronic heart failure: a multicenter, placebo-controlled trial.  In: Nicholls MG, ed. A Focus on the Clinical Effects of a Long Acting ACE-Inhibitors/Heart Failure . New York, NY: Raven Press; 1990;:31-40.
27 +
Giles TD, for Lisinopril Chronic Heart Failure Group.  Lisinopril treatment of congestive heart failure-results of a placebo controlled trial. Circulation . 1990;;82( (suppl 4) ):III-323. Abstract.
28 +
Rucinska EJ. Lisinopril First-Line Therapy in CHF . West Point, Pa: Merck Sharpe & Dohme Research Laboratories; September 1991;. Unpublished report.
29 +
Gilbert EM, Sandoval A, Larabee P, Renlund D, O'Connell JB, Bristow MR.  Lisinopril lowers cardiac adrenergic drive and increases β-receptor density in the failing human heart. Circulation . 1993;;88:472-480.
30 +
Lechat P, Garnham J, Desche P, Bounhoure JP.  Efficacy and acceptability of perindopril in mild to moderate chronic congestive heart failure. Am Heart J . 1993;;126:798-826.
31 +
Riegger GAJ.  The effects of ACE inhibitors on exercise capacity in the treatment of congestive heart failure. J Cardiovasc Pharmacol . 1990;;15 ( (suppl 2) ):41-46.
32 +
Northridge DB, Rose E, Elder A, et al.  A multicenter, double-blind, placebo-controlled trial of quinapril in mild chronic heart failure. Eur Heart J . 1991;;12( (suppl) ):184. Abstract.
33 +
Uprichard A.A 16-Week Double Blind, Placebo-Randomized Placebo Controlled Multicenter Trial to Evaluate the Effects of Withdrawal of Quinapril Hydrochloride on Exercise Tolerance in Patients With Mild to Moderate Congestive Heart Failure (906-276) . Ann Arbor, Mich: Parke-Davis Pharmaceutical Research; April 1994;. Unpublished report.
34 +
Uprichard A.  An 18-Week Double Blind, Optional Titration, Multicenter Study to Compare the Efficacy and Safety of Orally Administered Quinapril Hydrochloride With Captopril and Placebo in Patients With Congestive Heart Failure (906-226) . Ann Arbor, Mich: Parke-Davis Pharmaceutical Research; April 1994;. Unpublished report.
35 +
Uprichard A. A 12-Week Double Blind, Placebo Controlled Study to Determine the Efficacy and Safety of Orally Administered Quinapril Hydrochloride in Patients With Congestive Heart Failure (906-63) . Ann Arbor, Mich: Parke-Davis Pharmaceutical Research; April 1994;. Unpublished report.
36 +
Swedberg K, Amtorp O, Gundersen T, Remes J, Nilsson B.  Is maximal exercise testing a useful method to evaluate treatment of moderate heart failure? Circulation . 1991;;57:226. Abstract.
37 +
Maass L. Double-Blind Comparative Trial With Ramipril and Placebo in Patients With Heart Failure (NYHA Class III-IV) Stabilized on Digitalis and Furosemides . Frankfurt, Germany: Hoechst Aktiengesellschaft; October 1991;. Unpublished report.
38 +
Gordon M. Evaluation of the Efficacy and Safety of Ramipril (HOE 498) in Patients With Congestive Heart Failure in a Placebo-Controlled Trial . Somerville, NJ: Hoechst-Roussel Pharmaceuticals; October 1991;. Unpublished report.
39 +
Maass L. Efficacy and Safety of Ramipril (HOE 498) in Patients With Congestive Heart Failure in a Double Blind Placebo Controlled Trial . Frankfurt, Germany: Hoechst Aktiengesellschaft; October 1991;. Unpublished report.
40 +
Maass L. Evaluation of the Effect of Ramipril (HOE 498) on Exercise Duration, Invasive Cardiac Hemodynamics Profiles, and Safety in Patients With Congestive Heart Failure . Frankfurt, Germany: Hoechst Aktiengesellschaft; October 1991;. Unpublished report.
41 +
Lemarie JC. Multicenter Double-Blind Placebo-Controlled Study of the Efficacy and Safety of Ramipril Administered Orally for 24 Weeks in the Treatment of Stable Chronic Congestive Cardiac Failure . Paris, France: Laboratories Hoechst; December 1992;. Unpublished report.
42 +
Kramer BL, Massie BM, Topic N.  Controlled trial of captopril in chronic heart failure: a rest and exercise hemodynamic study. Circulation . 1983;;4: 807-816.
43 +
Captopril Multicenter Research Group.  A placebo controlled trial of captopril in refractory chronic congestive heart failure. J Am Coll Cardiol . 1983;; 2:755-763.
44 +
Chrysant SG, Gollub S, Dunn MI, Bal IS, Dreiling R, Konijeti JR.  Hemodynamic and metabolic effects of enalapril in patients with heart failure. Clin Cardiol . 1985;;8:585-590.
45 +
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.
46 +
Creager MA, Massie BM, Faxon DP, et al.  Acute and long-term effects of enalapril on the cardiovascular response to exercise and exercise tolerance in patients with congestive heart failure. J Am Coll Cardiol . 1985;;6:163-170.
47 +
Sharpe DN, Murphy J, Caxon R, Hannan SF.  Enalapril in patients with chronic heart failure: a placebo-controlled randomized, double-blind study. Circulation . 1984;;70:271-278.
48 +
Jenning G, Kiat H, Nelson L, Kelly MJ, Kalff V, Johns J.  Enalapril for severe congestive heart failure. Med J Aust . 1984;;141:723-726.
49 +
McGrath BPO, Arnolda L, Matthews PG, Jackson B, Jennings G, Kiat H, Johnson C.  Controlled trial of enalapril in congestive cardiac failure. Br Heart J . 1985;;54:405-414.
50 +
McGrath BP, Arnolda LF.  Enalapril reduces the catecholine response to exercise in patients with heart failure. Eur J Clin Pharmacol . 1986;; 30:485-487.
51 +
Joy M, Hubner PJ, Thomas RD, Cummin P, Dews I, William H, Shahrabani R.  Long-term use of enalapril in the treatment of patients with congestive heart failure. Int J Cardiol . 1987;;16:137-144.
52 +
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.
53 +
Webster MWJ, Fitzpatrick MA, Hamilton EJ, et al.  Effects of enalapril on clinical status, biochemistry, exercise performance and hemodynamics in heart failure. Drug . 1985;;30( (suppl I) ):74-81.
54 +
Lewis GR.  Comparison of lisinopril versus placebo for congestive heart failure. Am J Cardiol . 1989;;63:12D-16D.
55 +
Lewis GR.  Lisinopril versus placebo in older congestive heart failure. Am J Med . 1988;;85( (suppl 3B) ):48-54.
56 +
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( (suppl 3) ):S85-S97.
57 +
Giles TD.  Lisinopril in the treatment of congestive heart failure. J Hum Hypertens . 1989;;3:83-87.
58 +
Lechat P, Garnham SP, Desche P, Bounhoure JP.  Efficacy and acceptability of perindopril in mild to moderate chronic congestive heart failure. Am Heart J . 1993;;126:798-806.

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 +
References 1,2,8,11, 13-15,18-22, 24, 25, 28-30, 32-39.
2 +
References 1,2, 10-12, 14, 15, 22, 31, 32, 35, 39.
3 +
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.
4 +
The CONSENSUS Trial Study Group.  Effects of enalapril on mortality in severe congestive heart failure. N Engl J Med . 1987;;316:1429-1435.
5 +
Yusuf S, Peto R, Lewis J, Sleight P.  Beta-blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis . 1985;;17:335-371.
6 +
Early Breast Cancer Trialists' Collaborative Group.  Effect of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer. N Engl J Med . 1988;;319:1681-1692.
7 +
Held PH, Teo KK, Yusuf S.  Effects of beta-blockade, calcium channel blockers, and nitrates in acute myocardial infarction and unstable angina pectoris.  In: Topol EJ, ed. Textbook of Interventional Cardiology . Philadelphia, Pa: WB Saunders Co; 1991;:49-65.
8 +
DerSimonian R, Laird N.  Meta-analysis in clinical trials. Control Clin Trials . 1986;;7:177-188.
9 +
Mantel N, Haenszel W.  Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst . 1959;;22:719-748.
10 +
Colfer HT, Ribner HS, Gradman A, Hughes V, Kapoor A, Laideau JC, for the Benazepril Heart Failure Study Group.  Effects of once-daily benazepril therapy on exercise tolerance and manifestations of chronic congestive heart failure. Am J Cardiol . 1992;;70:354-358.
11 +
McGarry R. Randomized, Double Blind, Multicenter Study Comparing Benazepril to Digoxin and to Placebo as Add On Therapy to Diuretic in Patients With CHF, NYHA Class II-III During a 12-Week Treatment Period, GHBA-194 . Summit, NJ: Ciba-Geigy Pharmaceuticals; September 1991;. Unpublished report.
12 +
Magnani B, Magelli C, for the Multicenter Research Groups on Mild Heart Failure.  Captopril in mild heart failure: preliminary observations of a long-term double-blind, placebo-controlled multi centre trial. Postgrad Med J . 1986;;62( (suppl I) ):153-158.
13 +
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;;9( (suppl 2) ):S50-S60.
14 +
Captopril-Digoxin Multicenter Research Group.  Comparative effects of therapy with captopril and digoxin in patients with mild to moderate heart failure. JAMA . 1988;;259:539-544.
15 +
Newman TJ, Maskin CS, Dennick LG, Meyer JH, Hallows BG, Cooper WH.  Effects of captopril on survival in patients with heart failure. Am J Med . 1988;;84( (suppl 3A) ):140-144.
16 +
Barabino A, Galbariggi G, Pizzorni C, Lotti G.  Comparative effects of long-term therapy with captopril and ibopamine in chronic congestive heart failure in old patients. Cardiology . 1991;;78:289-296.
17 +
Kleber FX, Niemoller L, Doering W.  Impact of converting enzyme inhibition on progression of chronic heart failure: results of the Munich mild heart failure trial. Br Heart J . 1992;;67:289-296.
18 +
Niitani H, Hisakazu Y, Kawai C, et al.  Clinical study of captopril (CS-522 CHF) on chronic heart failure: multicenter double blind study in comparison with placebo [in Japanese]. Rinshioyaku . 1992;; 8:1273-1291.
19 +
Magnani B, Rizzon R. SCIC—Sopravivenza con Captopril nell' Insufficienza Cardiaca: Protocol . Bologna, Italy: SCIC—Sopravivenza con Captopril nell' Insufficienza Cardiaca; 1990;.
20 +
Drexler H, Banhardt BS, Meinertz T, Wollschlager H, Lehmann M, Just H.  Contrasting peripheral short-term and long-term effects of converting enzyme inhibition in patients with congestive heart failure: a double blind, placebo controlled trial. Circulation . 1989;;79:491-502.
21 +
Cleland JGF, Dargie HJ, Ball SG, et al.  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;;54: 305-311.
22 +
Rucinska EJ. A Double Blind Placebo Controlled Study to Evaluate the Effects of Enalapril in Patients With Chronic Heart Failure . West Point, Pa: Merck Sharpe & Dohme Research Laboratories; September 1991;. Unpublished report.
23 +
Enalapril CHF Investigators.  Long-term effects of enalapril in patients with congestive heart failure: a multicenter, placebo-controlled trial. Heart Failure . 1987;;3:102-107.
24 +
Dickstein K, Barvik S, Aarsland T.  Effect of long-term enalapril therapy on cardiopulmonary exercise performance in men with mild heart failure and previous myocardial infarction. J Am Coll Cardiol . 1991;;18:596-602.
25 +
Rucinska EJ. Enalapril vs Placebo in Previously Untreated Patients With CHF . West Point, Pa: Merck Sharpe & Dohme Research Laboratories; September 1991;. Unpublished report.
26 +
Zwehl W, Rucinska E, for Lisinopril Chronic Heart Failure Investigators.  Long-term effects of lisinopril in patients with chronic heart failure: a multicenter, placebo-controlled trial.  In: Nicholls MG, ed. A Focus on the Clinical Effects of a Long Acting ACE-Inhibitors/Heart Failure . New York, NY: Raven Press; 1990;:31-40.
27 +
Giles TD, for Lisinopril Chronic Heart Failure Group.  Lisinopril treatment of congestive heart failure-results of a placebo controlled trial. Circulation . 1990;;82( (suppl 4) ):III-323. Abstract.
28 +
Rucinska EJ. Lisinopril First-Line Therapy in CHF . West Point, Pa: Merck Sharpe & Dohme Research Laboratories; September 1991;. Unpublished report.
29 +
Gilbert EM, Sandoval A, Larabee P, Renlund D, O'Connell JB, Bristow MR.  Lisinopril lowers cardiac adrenergic drive and increases β-receptor density in the failing human heart. Circulation . 1993;;88:472-480.
30 +
Lechat P, Garnham J, Desche P, Bounhoure JP.  Efficacy and acceptability of perindopril in mild to moderate chronic congestive heart failure. Am Heart J . 1993;;126:798-826.
31 +
Riegger GAJ.  The effects of ACE inhibitors on exercise capacity in the treatment of congestive heart failure. J Cardiovasc Pharmacol . 1990;;15 ( (suppl 2) ):41-46.
32 +
Northridge DB, Rose E, Elder A, et al.  A multicenter, double-blind, placebo-controlled trial of quinapril in mild chronic heart failure. Eur Heart J . 1991;;12( (suppl) ):184. Abstract.
33 +
Uprichard A.A 16-Week Double Blind, Placebo-Randomized Placebo Controlled Multicenter Trial to Evaluate the Effects of Withdrawal of Quinapril Hydrochloride on Exercise Tolerance in Patients With Mild to Moderate Congestive Heart Failure (906-276) . Ann Arbor, Mich: Parke-Davis Pharmaceutical Research; April 1994;. Unpublished report.
34 +
Uprichard A.  An 18-Week Double Blind, Optional Titration, Multicenter Study to Compare the Efficacy and Safety of Orally Administered Quinapril Hydrochloride With Captopril and Placebo in Patients With Congestive Heart Failure (906-226) . Ann Arbor, Mich: Parke-Davis Pharmaceutical Research; April 1994;. Unpublished report.
35 +
Uprichard A. A 12-Week Double Blind, Placebo Controlled Study to Determine the Efficacy and Safety of Orally Administered Quinapril Hydrochloride in Patients With Congestive Heart Failure (906-63) . Ann Arbor, Mich: Parke-Davis Pharmaceutical Research; April 1994;. Unpublished report.
36 +
Swedberg K, Amtorp O, Gundersen T, Remes J, Nilsson B.  Is maximal exercise testing a useful method to evaluate treatment of moderate heart failure? Circulation . 1991;;57:226. Abstract.
37 +
Maass L. Double-Blind Comparative Trial With Ramipril and Placebo in Patients With Heart Failure (NYHA Class III-IV) Stabilized on Digitalis and Furosemides . Frankfurt, Germany: Hoechst Aktiengesellschaft; October 1991;. Unpublished report.
38 +
Gordon M. Evaluation of the Efficacy and Safety of Ramipril (HOE 498) in Patients With Congestive Heart Failure in a Placebo-Controlled Trial . Somerville, NJ: Hoechst-Roussel Pharmaceuticals; October 1991;. Unpublished report.
39 +
Maass L. Efficacy and Safety of Ramipril (HOE 498) in Patients With Congestive Heart Failure in a Double Blind Placebo Controlled Trial . Frankfurt, Germany: Hoechst Aktiengesellschaft; October 1991;. Unpublished report.
40 +
Maass L. Evaluation of the Effect of Ramipril (HOE 498) on Exercise Duration, Invasive Cardiac Hemodynamics Profiles, and Safety in Patients With Congestive Heart Failure . Frankfurt, Germany: Hoechst Aktiengesellschaft; October 1991;. Unpublished report.
41 +
Lemarie JC. Multicenter Double-Blind Placebo-Controlled Study of the Efficacy and Safety of Ramipril Administered Orally for 24 Weeks in the Treatment of Stable Chronic Congestive Cardiac Failure . Paris, France: Laboratories Hoechst; December 1992;. Unpublished report.
42 +
Kramer BL, Massie BM, Topic N.  Controlled trial of captopril in chronic heart failure: a rest and exercise hemodynamic study. Circulation . 1983;;4: 807-816.
43 +
Captopril Multicenter Research Group.  A placebo controlled trial of captopril in refractory chronic congestive heart failure. J Am Coll Cardiol . 1983;; 2:755-763.
44 +
Chrysant SG, Gollub S, Dunn MI, Bal IS, Dreiling R, Konijeti JR.  Hemodynamic and metabolic effects of enalapril in patients with heart failure. Clin Cardiol . 1985;;8:585-590.
45 +
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.
46 +
Creager MA, Massie BM, Faxon DP, et al.  Acute and long-term effects of enalapril on the cardiovascular response to exercise and exercise tolerance in patients with congestive heart failure. J Am Coll Cardiol . 1985;;6:163-170.
47 +
Sharpe DN, Murphy J, Caxon R, Hannan SF.  Enalapril in patients with chronic heart failure: a placebo-controlled randomized, double-blind study. Circulation . 1984;;70:271-278.
48 +
Jenning G, Kiat H, Nelson L, Kelly MJ, Kalff V, Johns J.  Enalapril for severe congestive heart failure. Med J Aust . 1984;;141:723-726.
49 +
McGrath BPO, Arnolda L, Matthews PG, Jackson B, Jennings G, Kiat H, Johnson C.  Controlled trial of enalapril in congestive cardiac failure. Br Heart J . 1985;;54:405-414.
50 +
McGrath BP, Arnolda LF.  Enalapril reduces the catecholine response to exercise in patients with heart failure. Eur J Clin Pharmacol . 1986;; 30:485-487.
51 +
Joy M, Hubner PJ, Thomas RD, Cummin P, Dews I, William H, Shahrabani R.  Long-term use of enalapril in the treatment of patients with congestive heart failure. Int J Cardiol . 1987;;16:137-144.
52 +
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.
53 +
Webster MWJ, Fitzpatrick MA, Hamilton EJ, et al.  Effects of enalapril on clinical status, biochemistry, exercise performance and hemodynamics in heart failure. Drug . 1985;;30( (suppl I) ):74-81.
54 +
Lewis GR.  Comparison of lisinopril versus placebo for congestive heart failure. Am J Cardiol . 1989;;63:12D-16D.
55 +
Lewis GR.  Lisinopril versus placebo in older congestive heart failure. Am J Med . 1988;;85( (suppl 3B) ):48-54.
56 +
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( (suppl 3) ):S85-S97.
57 +
Giles TD.  Lisinopril in the treatment of congestive heart failure. J Hum Hypertens . 1989;;3:83-87.
58 +
Lechat P, Garnham SP, Desche P, Bounhoure JP.  Efficacy and acceptability of perindopril in mild to moderate chronic congestive heart failure. Am Heart J . 1993;;126:798-806.

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To understand the clinical management of acute heart failure syndromes.
Accreditation Information The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
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For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
To view and print your certificate and access a summary of your CME courses go to My CME.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
Compression-Only CPR: Pushing the Science Forward
Cone
AAM 2010;304:1493-1495.
All you need to read in the other general journals
BMJ 2010;341:c5893-c1494.
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