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(Circulation. 1999;100:2312.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Comparative Effects of Low and High Doses of the Angiotensin-Converting Enzyme Inhibitor, Lisinopril, on Morbidity and Mortality in Chronic Heart Failure
From the College of Physicians and Surgeons (M.P.), Columbia University, New York, NY; Imperial College School of Medicine (P.A.P-W.), University of London, UK; University of Alberta (P.W.A.), Edmonton, Canada; University of Hull (J.G.F.C.), UK; University of Adelaide (J.H.), Australia; University of California (B.M.M.), San Francisco; Karolinska Institutet (L.R.), Stockholm, Sweden; Aarhus University Hospital (K.T.), Denmark; and University of Texas, Galveston (B.F.U).
Background—Angiotensin-converting enzyme (ACE) inhibitors are generally prescribed by physicians in doses lower than the large doses that have been shown to reduce morbidity and mortality in patients with heart failure. It is unclear, however, if low doses and high doses of ACE inhibitors have similar benefits.
Methods and Results—We randomly assigned 3164 patients with New
York Heart Association class II to IV heart failure and an ejection
fraction 
30% to double-blind treatment with either low doses (2.5 to
5.0 mg daily, n=1596) or high doses (32.5 to 35 mg daily, n=1568) of
the ACE inhibitor, lisinopril, for 39 to 58
months, while background therapy for heart failure was continued. When
compared with the low-dose group, patients in the high-dose group had a
nonsignificant 8% lower risk of death (P=0.128) but a
significant 12% lower risk of death or hospitalization for any reason
(P=0.002) and 24% fewer hospitalizations for heart
failure (P=0.002). Dizziness and renal insufficiency was
observed more frequently in the high-dose group, but the 2 groups were
similar in the number of patients requiring discontinuation of the
study medication.
Conclusions—These findings indicate that patients with heart failure should not generally be maintained on very low doses of an ACE inhibitor (unless these are the only doses that can be tolerated) and suggest that the difference in efficacy between intermediate and high doses of an ACE inhibitor (if any) is likely to be very small.
Key Words: heart failure • drugs • mortality • morbidity • trials
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F. J. Haddy, D. J. Campbell, W. E. Cayley Jr., J. C. Forfar, S. Munir, J. N. Cohn, and G. Tognoni Valsartan in Chronic Heart Failure N. Engl. J. Med., April 11, 2002; 346(15): 1173 - 1174. [Full Text] [PDF]
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C. A. J. Farquharson and A. D. Struthers Gradual reactivation over time of vascular tissue angiotensin I to angiotensin II conversion during chronic lisinopril therapy in chronic heart failure J. Am. Coll. Cardiol., March 6, 2002; 39(5): 767 - 775. [Abstract] [Full Text] [PDF]
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N. Lapointe and J.-L. Rouleau Activation of vascular tissue angiotensin-converting enzyme (ACE) in heart failure: Effects of ACE inhibitors J. Am. Coll. Cardiol., March 6, 2002; 39(5): 776 - 779. [Full Text] [PDF]
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R. Gradaus, S. Kerber, D. Bocker, H. H. Scheld, G. Breithardt, and M. C. Deng Therapeutic options and heart failure survival score predictability in an academic heart failure center: an analysis of 120 consecutive patients during a 1-year period Eur J Heart Fail, March 1, 2002; 4(2): 207 - 214. [Abstract] [Full Text] [PDF]
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A. Nohria, E. Lewis, and L. W. Stevenson Medical Management of Advanced Heart Failure JAMA, February 6, 2002; 287(5): 628 - 640. [Abstract] [Full Text] [PDF]
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W. H. Wilson Tang, R. H. Vagelos, Y.-G. Yee, C. R. Benedict, K. Willson, C. L. Liss, P. LaBelle, and M. B. Fowler Neurohormonal and clinical responses to high- versus low-dose enalapril therapy in chronic heart failure J. Am. Coll. Cardiol., January 2, 2002; 39(1): 70 - 78. [Abstract] [Full Text] [PDF]
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B. M. Massie Neurohormonal blockade in chronic heart failure: How much is enough? can there be too much? J. Am. Coll. Cardiol., January 2, 2002; 39(1): 79 - 82. [Full Text] [PDF]
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T. Elung-Jensen, J. Heisterberg, A.-L. Kamper, J. Sonne, S. Strandgaard, and N. E. Larsen High serum enalaprilat in chronic renal failure Journal of Renin-Angiotensin-Aldosterone System, December 1, 2001; 2(4): 240 - 245. [Abstract] [PDF]
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M.C. Petrie, C. Berry, S. Stewart, and J.J.V. McMurray Failing ageing hearts Eur. Heart J., November 1, 2001; 22(21): 1978 - 1990. [PDF]
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D. P. Holst, D. Kaye, M. Richardson, H. Krum, D. Prior, A. Aggarwal, R. Wolfe, and P. Bergin Improved outcomes from a comprehensive management system for heart failure Eur J Heart Fail, October 1, 2001; 3(5): 619 - 625. [Abstract] [Full Text] [PDF]
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P. Bovet, F. Paccaud, H. L. McLeod, F. A. Masoudi, E. P. Havranek, E. Ofili, J. Flack, G. Gibbons, D. V. Exner, M. J. Domanski, et al. Race and Responsiveness to Drugs for Heart Failure N. Engl. J. Med., September 6, 2001; 345(10): 766 - 768. [Full Text] [PDF]
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Task Force for the Diagnosis and Treatment of Chro, W. J. Remme, and K. Swedberg Guidelines for the diagnosis and treatment of chronic heart failure Eur. Heart J., September 1, 2001; 22(17): 1527 - 1560. [PDF]
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E. Weil and J. V. Tu Quality of congestive heart failure treatment at a Canadian teaching hospital Can. Med. Assoc. J., August 1, 2001; 165(3): 284 - 287. [Abstract] [Full Text] [PDF]
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N. Giannetti Management of congestive heart failure: How well are we doing? Can. Med. Assoc. J., August 1, 2001; 165(3): 305 - 306. [Full Text] [PDF]
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J. McMurray, A. Cohen-Solal, R. Dietz, E. Eichhorn, L. Erhardt, R. Hobbs, A. Maggioni, I. Pina, J. Soler-Soler, and K. Swedberg Practical recommendations for the use of ACE inhibitors, beta-blockers and spironolactone in heart failure: putting guidelines into practice Eur J Heart Fail, August 1, 2001; 3(4): 495 - 502. [Abstract] [Full Text] [PDF]
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C. Iribarren, A. J. Karter, A. S. Go, A. Ferrara, J. Y. Liu, S. Sidney, and J. V. Selby Glycemic Control and Heart Failure Among Adult Patients With Diabetes Circulation, June 5, 2001; 103(22): 2668 - 2673. [Abstract] [Full Text] [PDF]
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M. E. Khalil, A. W. Basher, E. J. Brown Jr, and I. A. Alhaddad A remarkable medical story: benefits of angiotensin-converting enzyme inhibitors in cardiac patients J. Am. Coll. Cardiol., June 1, 2001; 37(7): 1757 - 1764. [Abstract] [Full Text] [PDF]
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C. Berry, D. R. Murdoch, and J. J.V. McMurray Economics of chronic heart failure Eur J Heart Fail, June 1, 2001; 3(3): 283 - 291. [Abstract] [Full Text] [PDF]
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D. V. Exner, D. L. Dries, M. J. Domanski, and J. N. Cohn Lesser Response to Angiotensin-Converting-Enzyme Inhibitor Therapy in Black as Compared with White Patients with Left Ventricular Dysfunction N. Engl. J. Med., May 3, 2001; 344(18): 1351 - 1357. [Abstract] [Full Text] [PDF]
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F. H. H. Leenen and B. Yuan Prevention of Hypertension by Irbesartan in Dahl S Rats Relates to Central Angiotensin II Type 1 Receptor Blockade Hypertension, March 1, 2001; 37(3): 981 - 984. [Abstract] [Full Text] [PDF]
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M. W. Rich Heart Failure in the 21st Century: A Cardiogeriatric Syndrome J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2001; 56(2): 88M - 96. [Abstract] [Full Text]
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