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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
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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“The greater relative benefit for the composite primary endpoint (all-cause mortality or HF hospitalization) of high-dose lisinopril was similar in patients with and without T2DM.”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [143]
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ResultAn efficient method for accommodating potentially underpowered primary endpoints
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BackgroundManagement of patients with non-ischaemic cardiomyopathy
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Metadata
- 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
- Venue
- Circulation
- Published
- 1999-12-07
- Volume
- 100
- Issue
- 23
- Pages
- 2312-2318
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- 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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