This Article  • References  • Full text PDF  • Correction  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (906)  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Social Bookmarking   What's this?

Rekha Garg, MD, MS; Salim Yusuf, MBBS, FRCP, DPhil; the Collaborative Group on ACE Inhibitor Trials; 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

JAMA. 1995;273(18):1450-1456.

Abstract
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—Data were obtained for all completed, published or unpublished, randomized, placebo-controlled trials of ACE inhibitors that were at least 8 weeks in duration and had determined total mortality by intention to treat,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 Unpublished data were obtained by direct correspondence with the principal investigator of each study or pharmaceutical firm.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)

Author Affiliations
Klinikum der Universitat, Frankfurt, Germany; Oklahoma Cardiovascular and Hypertension Center, Oklahoma City; University of Genoa (Italy); Hammersmith Hospital, London, England; Brigham and Women's Hospital, Boston, Mass; Institut de Recherches Internationales Servier, Courbevoie, France; Central Hospital, Rogaland, Norway; University of Freiburg (Germany); CIBA-GEIGY Corp, Summit, NJ; Hoechst-Roussel Pharmaceutical, Somerville, NJ; Alfred Hospital and Baker Medical Unit, Melbourne, Australia; St Peter's Hospital, Chertsey, England; Ludwig Maximilian Universitat, Munich, Germany; Hoechst AG, Frankfurt, Germany; University of Bologna (Italy); Bristol-Myers Squibb, Princeton, NJ; Veterans Administration Medical Center, San Francisco, Calif; CIBA-GEIGY Corp, Summit, NJ; Monash Medical Center, Melbourne, Australia; Astra Hassle AB, Molndal, Sweden; Kuopio (Finland) University Hospital; Merck Human Health Division, West Point, Pa; University of Auckland (New Zealand); Goteborg (Sweden) University; Parke-Davis, Ann Arbor, Mich. Facilitators; (chair), University of Michigan, Ann Arbor; Universita degli Studi di Bologna (Italy); Oxford (England) University; Brigham and Women's Hospital, Boston, Mass; Oxford (England) University; Goteborg (Sweden) University; Instituto M. Negri, Milan, Italy

Klinikum der Universitat, Frankfurt, Germany; Oxford (England) University

From the Clinical Trials Branch, National Heart, Lung, and Blood Institute, Bethesda, Md (Dr Garg), and the Division of Cardiology, Hamilton General Hospital, McMaster University, Hamilton, Ontario (Dr Yusuf). Dr Yusuf is a Career Scientist of the Medical Research Council of Canada.

Footnotes
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).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Efficacy and safety of different techniques of paravertebral block for analgesia after thoracotomy: a systematic review and metaregression
Kotze et al.
Br J Anaesth 2009;103:626-636.
ABSTRACT | FULL TEXT  

Systematic Review: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II-Receptor Blockers for Ischemic Heart Disease
Baker et al.
ANN INTERN MED 2009;0:0000605-200912150-00162v1-E-162.
ABSTRACT | FULL TEXT  

A prospective longitudinal evaluation of the benefits of epicardial lead placement for cardiac resynchronization therapy
Patwala et al.
Europace 2009;11:1323-1329.
ABSTRACT | FULL TEXT  

Heart failure in women: a need for prospective data.
Hsich and Pina
J Am Coll Cardiol 2009;54:491-498.
ABSTRACT | FULL TEXT  

Effect of piboserod, a 5-HT4 serotonin receptor antagonist, on left ventricular function in patients with symptomatic heart failure
Kjekshus et al.
Eur J Heart Fail 2009;11:771-778.
ABSTRACT | FULL TEXT  

Palliative care in congestive heart failure.
Goodlin
J Am Coll Cardiol 2009;54:386-396.
ABSTRACT | FULL TEXT  

Cardiac 12/15 lipoxygenase-induced inflammation is involved in heart failure
Kayama et al.
JEM 2009;206:1565-1574.
ABSTRACT | FULL TEXT  

Diagnosis and treatment of acquired coronary artery disease in adults
Wilson
Postgrad. Med. J. 2009;85:364-365.
ABSTRACT | FULL TEXT  

Effects of enalapril or nifedipine on muscle strength or functional capacity in elderly subjects. A double blind trial
Bunout et al.
Journal of Renin-Angiotensin-Aldosterone System 2009;10:77-84.
ABSTRACT  

2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation
Hunt et al.
J Am Coll Cardiol 2009;53:e1-e90.
FULL TEXT  

2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation
Jessup et al.
J Am Coll Cardiol 2009;53:1343-1382.
FULL TEXT  

2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation
2009 WRITING GROUP TO REVIEW NEW EVIDENCE AND UPDA et al.
Circulation 2009;119:1977-2016.
FULL TEXT  

2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation
2005 WRITING COMMITTEE MEMBERS et al.
Circulation 2009;119:e391-e479.
FULL TEXT  

Clinical burden and health service challenges of chronic heart failure
Hobbs
Eur J Heart Fail Suppl 2009;8:i1-i4.
FULL TEXT  

Randomized Trial of Warfarin, Aspirin, and Clopidogrel in Patients With Chronic Heart Failure: The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) Trial
Massie et al.
Circulation 2009;119:1616-1624.
ABSTRACT | FULL TEXT  

Survival trends in men and women with heart failure of ischaemic and non-ischaemic origin: data for the period 1987-2003 from the Swedish Hospital Discharge Registry
Shafazand et al.
Eur Heart J 2009;30:671-678.
ABSTRACT | FULL TEXT  

Right ventricular dilatation predicts survival after mitral valve repair in patients with impaired left ventricular systolic function
Chrustowicz et al.
Eur J Echocardiogr 2009;10:309-313.
ABSTRACT | FULL TEXT  

The current role of beta-blockers in chronic heart failure: with special emphasis on the CIBIS III trial
Willenheimer
Eur Heart J Suppl 2009;11:A15-A20.
ABSTRACT | FULL TEXT  

Long-Term Trends in First Hospitalization for Heart Failure and Subsequent Survival Between 1986 and 2003: A Population Study of 5.1 Million People
Jhund et al.
Circulation 2009;119:515-523.
ABSTRACT | FULL TEXT  

Can trial sequential monitoring boundaries reduce spurious inferences from meta-analyses?
Thorlund et al.
Int J Epidemiol 2009;38:276-286.
ABSTRACT | FULL TEXT  

Mode of death in patients with newly diagnosed heart failure in the general population
Mehta et al.
Eur J Heart Fail 2008;10:1108-1116.
ABSTRACT | FULL TEXT  

Enalapril and captopril increased mortality compared with ramipril in elderly patients with heart failure
Rideout
Evid. Based Nurs. 2008;11:123-123.
FULL TEXT  

Heart Failure-Related Hospitalization in the U.S., 1979 to 2004
Fang et al.
J Am Coll Cardiol 2008;52:428-434.
ABSTRACT | FULL TEXT  

ACE-inhibitor, AT1-receptor-antagonist, or both? A clinical pharmacologist`s perspective after publication of the results of ONTARGET
Schindler
Ther Adv Cardiovasc Dis 2008;2:233-248.
ABSTRACT  

Racial Analysis of Patients With Myocardial Infarction Complicated by Heart Failure and/or Left Ventricular Dysfunction Treated With Valsartan, Captopril, or Both
Prisant et al.
J Am Coll Cardiol 2008;51:1865-1871.
ABSTRACT | FULL TEXT  

Effect of different angiotensin-converting-enzyme inhibitors on mortality among elderly patients with congestive heart failure
Pilote et al.
CMAJ 2008;178:1303-1311.
ABSTRACT | FULL TEXT  

Comparative effectiveness of angiotensin-converting-enzyme inhibitors: Is an ACE always an ace?
Hernandez and Harrington
CMAJ 2008;178:1316-1319.
FULL TEXT  

Feasibility and clinical decision-making with 3D echocardiography in routine practice
Hare et al.
Heart 2008;94:440-445.
ABSTRACT | FULL TEXT  

Mice expressing ACE only in the heart show that increased cardiac angiotensin II is not associated with cardiac hypertrophy
Xiao et al.
Am. J. Physiol. Heart Circ. Physiol. 2008;294:H659-H667.
ABSTRACT | FULL TEXT  

Experimental and clinical basis for the use of statins in patients with ischemic and nonischemic cardiomyopathy.
Ramasubbu et al.
J Am Coll Cardiol 2008;51:415-426.
ABSTRACT | FULL TEXT  

ARBs Outperform ACE Inhibitors in Women With Heart Failure
Law
DOC News 2007;4:10-10.
FULL TEXT  

Adverse Effects of Combination Angiotensin II Receptor Blockers Plus Angiotensin-Converting Enzyme Inhibitors for Left Ventricular Dysfunction: A Quantitative Review of Data From Randomized Clinical Trials
Phillips et al.
Arch Intern Med 2007;167:1930-1936.
ABSTRACT | FULL TEXT  

Beneficial Effects of Complement Inhibition With Soluble Complement Receptor 1 (TP10) During Cardiac Surgery: Is There a Gender Difference?
Lazar et al.
Circulation 2007;116:I-83-I-88.
ABSTRACT | FULL TEXT  

Perindopril preserves left ventricular function in X-linked Duchenne muscular dystrophy
Duboc et al.
Eur Heart J Suppl 2007;9:E20-E24.
ABSTRACT | FULL TEXT  

Learning From a Real-World Analysis of Implantable Cardioverter-Defibrillator Recipients: Comorbidities Matter
Chugh et al.
J Am Coll Cardiol 2007;49:2416-2418.
FULL TEXT  

Angiotensin-converting enzyme inhibitors and survival in women and men with heart failure
Keyhan et al.
Eur J Heart Fail 2007;9:594-601.
ABSTRACT | FULL TEXT  

Prognosis of all-cause heart failure and borderline left ventricular systolic dysfunction: 5 year mortality follow-up of the Echocardiographic Heart of England Screening Study (ECHOES)
Hobbs et al.
Eur Heart J 2007;28:1128-1134.
ABSTRACT | FULL TEXT  

Medicare's Hospital Compare Performance Measures and Mortality Rates
Shekelle
JAMA 2007;297:1430-1431.
FULL TEXT  

Early and Sustained Benefit on Event-Free Survival and Heart Failure Hospitalization From Fixed-Dose Combination of Isosorbide Dinitrate/Hydralazine: Consistency Across Subgroups in the African-American Heart Failure Trial
Taylor et al.
Circulation 2007;115:1747-1753.
ABSTRACT | FULL TEXT  

A comprehensive view of sex-specific issues related to cardiovascular disease
Pilote et al.
CMAJ 2007;176:S1-S44.
ABSTRACT | FULL TEXT  

Review: Lisinopril in paediatric medicine: a retrospective chart review of long-term treatment in children
Raes et al.
Journal of Renin-Angiotensin-Aldosterone System 2007;8:3-12.
ABSTRACT  

Diabetic Cardiovascular Autonomic Neuropathy
Vinik and Ziegler
Circulation 2007;115:387-397.
FULL TEXT  

Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system
Mehta and Griendling
Am. J. Physiol. Cell Physiol. 2007;292:C82-C97.
ABSTRACT | FULL TEXT  

Concordance with heart failure medications: what do patients think?
Hobbs
Fam Pract 2006;23:607-608.
FULL TEXT  

Effects of cardiac resynchronization therapy on overall mortality and mode of death: a meta-analysis of randomized controlled trials
Rivero-Ayerza et al.
Eur Heart J 2006;27:2682-2688.
ABSTRACT | FULL TEXT  

Exercise and Respiratory Training Improve Exercise Capacity and Quality of Life in Patients With Severe Chronic Pulmonary Hypertension
Mereles et al.
Circulation 2006;114:1482-1489.
ABSTRACT | FULL TEXT  

A commentary on clinical trials in chronic heart failure.
Poole-Wilson et al.
SEMIN CARDIOTHORAC VASC ANESTH 2006;10:242-245.
ABSTRACT  

Chronic Obstructive Pulmonary Disease, Risk Factors, and Outcome Trials: Comparisons with Cardiovascular Disease
Ramsey and Hobbs
Proc Am Thorac Soc 2006;3:635-640.
ABSTRACT | FULL TEXT  

Perioperative management of chronic heart failure.
Groban and Butterworth
Anesth. Analg. 2006;103:557-575.
ABSTRACT | FULL TEXT  

The population mortality benefits of maximizing the number of eligible patients receiving appropriate cardiology treatments in Ireland
Kabir et al.
QJM 2006;99:523-530.
ABSTRACT | FULL TEXT  

NTproBNP-guided drug treatment for chronic heart failure: design and methods in the "BATTLESCARRED" trial
Lainchbury et al.
Eur J Heart Fail 2006;8:532-538.
ABSTRACT | FULL TEXT  

A rapid access cardiology service for chest pain, heart failure and arrhythmias accurately diagnoses cardiac disease and identifies patients at high risk: a prospective cohort study
Tenkorang et al.
Heart 2006;92:1084-1090.
ABSTRACT | FULL TEXT  

The evolution of heart failure management over recent decades: from CONSENSUS to CIBIS
Lechat
Eur Heart J Suppl 2006;8:C5-C12.
ABSTRACT | FULL TEXT  

Rationale and design of CIBIS III
Ponikowski
Eur Heart J Suppl 2006;8:C35-C42.
ABSTRACT | FULL TEXT  

How to begin treatment in chronic heart failure? Results of CIBIS III
Willenheimer
Eur Heart J Suppl 2006;8:C43-C50.
ABSTRACT | FULL TEXT  

Accuracy of B-type natriuretic Peptide tests to exclude congestive heart failure: systematic review of test accuracy studies.
Battaglia et al.
Arch Intern Med 2006;166:1073-1080.
ABSTRACT | FULL TEXT  

Gender and heart failure: a population perspective
Mehta and Cowie
Heart 2006;92:iii14-iii18.
FULL TEXT  

The Seattle Heart Failure Model: Prediction of Survival in Heart Failure
Levy et al.
Circulation 2006;113:1424-1433.
ABSTRACT | FULL TEXT  

Aldosterone Blockade Over and Above ACE-Inhibitors in Patients with Coronary Artery Disease but without Heart Failure
Shah et al.
Journal of Renin-Angiotensin-Aldosterone System 2006;7:20-30.
ABSTRACT  

Protecting the Heart with Cardiac Medication in Patients with Left Ventricular Dysfunction Undergoing Major Noncardiac Vascular Surgery
Feringa et al.
SEMIN CARDIOTHORAC VASC ANESTH 2006;10:25-31.
ABSTRACT  

Changing Incidence and Survival for Heart Failure in a Well-Defined Older Population, 1970-1974 and 1990-1994
Barker et al.
Circulation 2006;113:799-805.
ABSTRACT | FULL TEXT  

Cost-Effectiveness of Hospital Pay-for-Performance Incentives
Nahra et al.
Med Care Res Rev 2006;63:49S-72S.
ABSTRACT  

Epidemiology of heart failure in a community-based study of subjects aged >=57 years: Incidence and long-term survival
van Jaarsveld et al.
Eur J Heart Fail 2006;8:23-30.
ABSTRACT | FULL TEXT  

Kidney-Heart Interactions: Epidemiology, Pathogenesis, and Treatment
Berl and Henrich
CJASN 2006;1:8-18.
FULL TEXT  

Utilization of evidence-based therapies for heart failure in the institutionalized elderly
Shibata et al.
Eur J Heart Fail 2005;7:1122-1125.
ABSTRACT | FULL TEXT  

JBS 2: Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice
Prepared by: British Cardiac Society, British Hype
Heart 2005;91:v1-v52.
FULL TEXT  

Mortality and Morbidity Remain High Despite Captopril and/or Valsartan Therapy in Elderly Patients With Left Ventricular Systolic Dysfunction, Heart Failure, or Both After Acute Myocardial Infarction: Results From the Valsartan in Acute Myocardial Infarction Trial (VALIANT)
White et al.
Circulation 2005;112:3391-3399.
ABSTRACT | FULL TEXT  

Angiotensin-Converting Enzyme Inhibitors or {beta}-Blockers in Heart Failure: Does It Matter Who Goes First?
Fang
Circulation 2005;112:2380-2382.
FULL TEXT  

Effect on Survival and Hospitalization of Initiating Treatment for Chronic Heart Failure With Bisoprolol Followed by Enalapril, as Compared With the Opposite Sequence: Results of the Randomized Cardiac Insufficiency Bisoprolol Study (CIBIS) III
Willenheimer et al.
Circulation 2005;112:2426-2435.
ABSTRACT | FULL TEXT  

Explaining the Decline in Coronary Heart Disease Mortality in Finland between 1982 and 1997
Laatikainen et al.
Am J Epidemiol 2005;162:764-773.
ABSTRACT | FULL TEXT  

Prognostic benefit of beta-blockers in patients not receiving ACE-Inhibitors
Krum et al.
Eur Heart J 2005;26:2154-2158.
ABSTRACT | FULL TEXT  

Risk-Treatment Mismatch in the Pharmacotherapy of Heart Failure
Lee et al.
JAMA 2005;294:1240-1247.
ABSTRACT | FULL TEXT  

Review: Dual blockade of the renin angiotensin system in diabetes -- rationale and risks
Kumar and Winocour
British Journal of Diabetes & Vascular Disease 2005;5:266-271.
ABSTRACT  

Implications of CIBIS III: A Commentary
Willenheimer
Journal of Renin-Angiotensin-Aldosterone System 2005;6:115-120.
ABSTRACT  

Long-Term Effects of Ramipril on Cardiovascular Events and on Diabetes: Results of the HOPE Study Extension
HOPE/HOPE-TOO Study Investigators
Circulation 2005;112:1339-1346.
ABSTRACT | FULL TEXT  

Female-specific aspects in the pharmacotherapy of chronic cardiovascular diseases
Jochmann et al.
Eur Heart J 2005;26:1585-1595.
ABSTRACT | FULL TEXT  

The diagnosis of heart failure in European primary care: The IMPROVEMENT Programme survey of perception and practice
Hobbs et al.
Eur J Heart Fail 2005;7:768-779.
ABSTRACT | FULL TEXT  

Contradicted and Initially Stronger Effects in Highly Cited Clinical Research
Ioannidis
JAMA 2005;294:218-228.
ABSTRACT | FULL TEXT  

Prevention of Atrial Fibrillation With Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: A Meta-Analysis
Healey et al.
J Am Coll Cardiol 2005;45:1832-1839.
ABSTRACT | FULL TEXT  

Persistent Cardiac Aldosterone Synthesis in Angiotensin II Type 1A Receptor-Knockout Mice After Myocardial Infarction
Katada et al.
Circulation 2005;111:2157-2164.
ABSTRACT | FULL TEXT  

Six minute corridor walk test as an outcome measure for the assessment of treatment in randomized, blinded intervention trials of chronic heart failure: a systematic review
Olsson et al.
Eur Heart J 2005;26:778-793.
ABSTRACT | FULL TEXT  

Pharmacotherapy of Congestive Heart Failure in Elderly Patients
Burger and Rocca
J CARDIOVASC PHARMACOL THER 2005;10:85-94.
ABSTRACT  

Effect of perindopril on the onset and progression of left ventricular dysfunction in Duchenne muscular dystrophy
Duboc et al.
J Am Coll Cardiol 2005;45:855-857.
ABSTRACT | FULL TEXT  

Factors influencing medical treatment of heart failure patients in Spanish internal medicine departments: a national survey
Roman-Sanchez et al.
QJM 2005;98:127-138.
ABSTRACT | FULL TEXT  

Narrative Review: Pharmacotherapy for Chronic Heart Failure: Evidence from Recent Clinical Trials
Yan et al.
ANN INTERN MED 2005;142:132-145.
ABSTRACT | FULL TEXT  

The Shocking Story of Azimilide
Hanna and Langberg
Circulation 2004;110:3624-3626.
FULL TEXT