Published Online
on February 24, 2003

A more recent version of this article appeared on March 11, 2003

This Article Full Text (PDF) All Versions of this Article: 107/9/1284    most recent 01.CIR.0000054165.93055.42v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Arnold, J. M. O. Search for Related Content PubMed PubMed Citation Articles by Arnold, J. M. O. Related Collections Congestive Cardiovascular Pharmacology Secondary prevention Clinical Studies Epidemiology Related Article

Submitted on June 17, 2002
Revised on December 5, 2002
Accepted on December 5, 2002

Prevention of Heart Failure in Patients in the Heart Outcomes Prevention Evaluation (HOPE) Study

J. Malcolm O. Arnold MD^*, Salim Yusuf MD, James Young MD, James Mathew MD, David Johnstone MD, Alvaro Avezum MD, Eva Lonn MD, Janice Pogue MSc, Jackie Bosch MSc, and on behalf of the HOPE Investigators

From London Health Sciences Centre (J.M.O.A.), London, Canada; Hamilton General Hospital (S.Y., E.L., J.P., J.B.), Hamilton, Canada; Cleveland Clinic (J.Y.), Cleveland, Ohio; University of Iowa College of Medicine (J.M.), Iowa City, Iowa; Dalhousie University (D.J.), Halifax, Canada; and Dante Pazzanese Cardiology Institute (A.A.), São Paulo, Brazil.

^* To whom correspondence should be addressed. E-mail: malcolm.arnold{at}lhsc.on.ca.

Background--Previous trials in the prevention of heart failure have been restricted to patients with low ejection fraction or hypertension. We assessed an angiotensin-converting enzyme (ACE) inhibitor, ramipril, to prevent the development of heart failure in high-risk patients without known low ejection fraction or heart failure.

Methods and Results--We randomly assigned 9297 patients to receive double-blind ramipril (10 mg daily) or matching placebo for 4.5 years. Death attributable to heart failure, hospitalization for heart failure, initiation of open-label ACE inhibitor for heart failure, or development of typical signs or symptoms of heart failure developed in 951 patients and was associated with a 4.01-fold increase in the risk of death (P<0.0001). The rate of developing heart failure was significantly increased with coronary disease (risk ratio, 2.17), microalbuminuria (1.82), left ventricular hypertrophy (1.47), increasing age (by decade, 1.37), and diabetes (1.36). Ramipril reduced new-onset heart failure rate from 11.5% to 9.0% (relative risk, 0.77; 95% CI, 0.68 to 0.87; P<0.0001). Ramipril consistently reduced heart failure rate both in those with (relative risk, 0.87) and those without an interim myocardial infarction (relative risk, 0.78). Ramipril also reduced the heart failure rate more in patients with baseline systolic pressure above the median (139 mm Hg) (relative risk, 0.67) compared with those below the median (relative risk, 0.91; P=0.024 for interaction of group by treatment).

Conclusion--Ramipril significantly reduces the rate of development of heart failure in patients at high risk of cardiovascular events.

Key words: heart failure • prevention • drugs • atherosclerosis • trials

Related Article:

Drug Therapy and Heart Failure Prevention

Jennifer V. Linseman and Michael R. Bristow
Circulation 2003 107: 1234-1236. [Extract] [Full Text]

This article has been cited by other articles:

				E. F. Lewis, S. D. Solomon, K. A. Jablonski, M. M. Rice, F. Clemenza, J. Hsia, A. P. Maggioni, M. Zabalgoitia, T. Huynh, T. E. Cuddy, et al. Predictors of Heart Failure in Patients With Stable Coronary Artery Disease: A PEACE Study Circ Heart Fail, May 1, 2009; 2(3): 209 - 216. [Abstract] [Full Text] [PDF]

				B. M. Massie, P. E. Carson, J. J. McMurray, M. Komajda, R. McKelvie, M. R. Zile, S. Anderson, M. Donovan, E. Iverson, C. Staiger, et al. Irbesartan in Patients with Heart Failure and Preserved Ejection Fraction N. Engl. J. Med., December 4, 2008; 359(23): 2456 - 2467. [Abstract] [Full Text] [PDF]

				C. M. Werner and M. Bohm Review: The therapeutic role of RAS blockade in chronic heart failure Therapeutic Advances in Cardiovascular Disease, June 1, 2008; 2(3): 167 - 177. [Abstract] [PDF]

				S. J. Lester, A. J. Tajik, R. A. Nishimura, J. K. Oh, B. K. Khandheria, and J. B. Seward Unlocking the Mysteries of Diastolic Function Deciphering the Rosetta Stone 10 Years Later. J. Am. Coll. Cardiol., February 19, 2008; 51(7): 679 - 689. [Abstract] [Full Text] [PDF]

				P. M. Okin, R. B. Devereux, K. E. Harris, S. Jern, S. E. Kjeldsen, S. Julius, J. M. Edelman, B. Dahlof, and for the LIFE Study Investigators Regression of Electrocardiographic Left Ventricular Hypertrophy Is Associated with Less Hospitalization for Heart Failure in Hypertensive Patients Ann Intern Med, September 4, 2007; 147(5): 311 - 319. [Abstract] [Full Text] [PDF]

				R. Maharaj Adding cost to number needed to treat: the COPE statistic Evid. Based Med., August 1, 2007; 12(4): 101 - 102. [Full Text] [PDF]

				E. Ingelsson, J. Sundstrom, L. Lind, U. Riserus, A. Larsson, S. Basu, and J. Arnlov Low-grade albuminuria and the incidence of heart failure in a community-based cohort of elderly men Eur. Heart J., July 2, 2007; 28(14): 1739 - 1745. [Abstract] [Full Text] [PDF]

				J. C. Coons and T. Fera Multidisciplinary team for enhancing care for patients with acute myocardial infarction or heart failure Am. J. Health Syst. Pharm., June 15, 2007; 64(12): 1274 - 1278. [Abstract] [Full Text] [PDF]

				S. Klotz, A.H. J. Danser, R. F. Foronjy, M. C. Oz, J. Wang, D. Mancini, J. D'Armiento, and D. Burkhoff The Impact of Angiotensin-Converting Enzyme Inhibitor Therapy on the Extracellular Collagen Matrix During Left Ventricular Assist Device Support in Patients With End-Stage Heart Failure J. Am. Coll. Cardiol., March 20, 2007; 49(11): 1166 - 1174. [Abstract] [Full Text] [PDF]

				K. Fox, R. Ferrari, S. Yusuf, and J. S. Borer Should angiotensin-converting enzyme-inhibitors be used to improve outcome in patients with coronary artery disease and 'preserved' left ventricular function? Eur. Heart J., September 2, 2006; 27(18): 2154 - 2157. [Abstract] [Full Text] [PDF]

				L. Groban and J. Butterworth Perioperative management of chronic heart failure. Anesth. Analg., September 1, 2006; 103(3): 557 - 575. [Abstract] [Full Text] [PDF]

				P. M. Okin, R. B. Devereux, M. S. Nieminen, S. Jern, L. Oikarinen, M. Viitasalo, L. Toivonen, S. E. Kjeldsen, B. Dahlof, and for the LIFE Study Investigators Electrocardiographic Strain Pattern and Prediction of New-Onset Congestive Heart Failure in Hypertensive Patients: The Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) Study Circulation, January 3, 2006; 113(1): 67 - 73. [Abstract] [Full Text] [PDF]

				M. R. Weir, K. C. Ferdinand, J. M. Flack, K. A. Jamerson, W. Daley, S. Zelenkofske, and for the AADVANCE Investigators A Noninferiority Comparison of Valsartan/Hydrochlorothiazide Combination Versus Amlodipine in Black Hypertensives Hypertension, September 1, 2005; 46(3): 508 - 513. [Abstract] [Full Text] [PDF]

				K. Berenji, M. H. Drazner, B. A. Rothermel, and J. A. Hill Does load-induced ventricular hypertrophy progress to systolic heart failure? Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H8 - H16. [Abstract] [Full Text] [PDF]

				T. Y. Wong, W. Rosamond, P. P. Chang, D. J. Couper, A. R. Sharrett, L. D. Hubbard, A. R. Folsom, and R. Klein Retinopathy and Risk of Congestive Heart Failure JAMA, January 5, 2005; 293(1): 63 - 69. [Abstract] [Full Text] [PDF]

				Task Force Members, J. Lopez-Sendon, K. Swedberg, J. McMurray, J. Tamargo, A. P. Maggioni, H. Dargie, M. Tendera, F. Waagstein, J. Kjekshus, et al. Expert consensus document on angiotensin converting enzyme inhibitors in cardiovascular disease: The Task Force on ACE-inhibitors of the European Society of Cardiology Eur. Heart J., August 2, 2004; 25(16): 1454 - 1470. [Full Text] [PDF]

				E. Lonn, R. Shaikholeslami, Q. Yi, J. Bosch, B. Sullivan, P. Tanser, A. Magi, and S. Yusuf Effects of ramipril on left ventricular mass and function in cardiovascular patients with controlled blood pressure and with preserved left ventricular ejection fraction: A substudy of the Heart Outcomes Prevention Evaluation (HOPE) trial J. Am. Coll. Cardiol., June 16, 2004; 43(12): 2200 - 2206. [Abstract] [Full Text] [PDF]

				D. S.H. Bell Diabetic Cardiomyopathy Diabetes Care, October 1, 2003; 26(10): 2949 - 2951. [Full Text] [PDF]

				D. Fitchett More than just hype Can. Med. Assoc. J., June 24, 2003; 168(13): 1646 - 1647. [Full Text] [PDF]

				J. V. Linseman and M. R. Bristow Drug Therapy and Heart Failure Prevention Circulation, March 11, 2003; 107(9): 1234 - 1236. [Full Text] [PDF]