Cited by 1,244Heart Failure Treatment and ManagementHeart rate and cardiovascular healthRenin-Angiotensin System Studies

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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.·1999·Circulation

DOI 10.1161/01.cir.100.23.2312

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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 < or = 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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Background

Authors: Packer, M., Poole-Wilson, P. A., Armstrong, P. W., Cleland, J. G. F., Horowitz, J. D., Massie, B. M., Rydén, L., Thygesen, K., & Uretsky, B. F.
Affiliations: University of London (GB)
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).
ORCID: Packer, Milton
Armstrong, Paul W.
Cleland, John G. F.
Horowitz, John D.
Thygesen, Kristian
Uretsky, Barry F.
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1999-12-07
Volume: 100
Issue: 23
Pages: 2312-2318
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/01.cir.100.23.2312
OpenAlex: W2129711762
Cited by: 1,244
References: 23
Citations by year: 2026: 19 · 2025: 31 · 2024: 38 · 2023: 50 · 2022: 60 · 2021: 40 · 2020: 47 · 2019: 44 · 2018: 48 · 2017: 52 · 2016: 55 · 2015: 43 · 2014: 33 · 2013: 36 · 2012: 36
FWCI: 45.44
Type: journal article
Language: en
Open access: closed
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Keywords: lisinopril, ACE inhibitors, chronic heart failure, dose comparison, low-dose therapy, high-dose therapy, mortality, hospitalization, ejection fraction, adverse effects, dizziness, renal failure
MeSH terms: Aged, Angiotensin-Converting Enzyme Inhibitors, Death, Double-Blind Method, Female, Heart Failure, Hospitalization, Humans, Male, Middle Aged, Morbidity, Survival Analysis, Lisinopril

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Comparative Effects of Low and High Doses of the Angiotensin-Converting Enzyme Inhibitor, Lisinopril, on Morbidity and Mortality in Chronic Heart Failure

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