Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure

Milton Packer, Philip A. Poole-Wilson, Paul W. Armstrong, John G F Cleland, John D. Horowitz, Barry M. Massie, Lars Rydén, Kristian Thygesen, Barry F. Uretsky

Research output: Contribution to journalArticle

926 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2312-2318
Number of pages7
JournalCirculation
Volume100
Issue number23
StatePublished - Dec 7 1999

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Lisinopril
Angiotensin-Converting Enzyme Inhibitors
Heart Failure
Morbidity
Mortality
Hospitalization
Dizziness
Renal Insufficiency
Physicians
Therapeutics

Keywords

  • Drugs
  • Heart failure
  • Morbidity
  • Mortality
  • Trials

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Packer, M., Poole-Wilson, P. A., Armstrong, P. W., Cleland, J. G. F., Horowitz, J. D., Massie, B. M., ... Uretsky, B. F. (1999). Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. Circulation, 100(23), 2312-2318.

Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. / Packer, Milton; Poole-Wilson, Philip A.; Armstrong, Paul W.; Cleland, John G F; Horowitz, John D.; Massie, Barry M.; Rydén, Lars; Thygesen, Kristian; Uretsky, Barry F.

In: Circulation, Vol. 100, No. 23, 07.12.1999, p. 2312-2318.

Research output: Contribution to journalArticle

Packer, M, Poole-Wilson, PA, Armstrong, PW, Cleland, JGF, Horowitz, JD, Massie, BM, Rydén, L, Thygesen, K & Uretsky, BF 1999, 'Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure', Circulation, vol. 100, no. 23, pp. 2312-2318.
Packer M, Poole-Wilson PA, Armstrong PW, Cleland JGF, Horowitz JD, Massie BM et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. Circulation. 1999 Dec 7;100(23):2312-2318.
Packer, Milton ; Poole-Wilson, Philip A. ; Armstrong, Paul W. ; Cleland, John G F ; Horowitz, John D. ; Massie, Barry M. ; Rydén, Lars ; Thygesen, Kristian ; Uretsky, Barry F. / Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. In: Circulation. 1999 ; Vol. 100, No. 23. pp. 2312-2318.
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abstract = "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.",
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AU - Cleland, John G F

AU - Horowitz, John D.

AU - Massie, Barry M.

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N2 - 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.

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