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

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 +1 more·1999·Circulation
DOI 10.1161/01.cir.100.23.2312
Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1161/01.cir.100.23.2312

Cites

24 of 24 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review