DOI: 10.1161/01.cir.100.23.2312. Comparative Effects of Low and High Doses of the Angiotensin-Converting Enzyme Inhibitor, Lisinopril, on Morbidity and Mortality in Chronic Heart Failure

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

10.1161/01.cir.100.23.2312

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Circulation (276)

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.

Bibliography

Packer, M., Poole-Wilson, P. A., Armstrong, P. W., Cleland, J. G. F., Horowitz, J. D., Massie, B. M., RydeÌn, L., Thygesen, K., & 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), 2312â2318.

Authors 9

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

References 18 Referenced 935

10.1161/circ.92.9.2764
10.1093/oxfordjournals.eurheartj.a015339
10.1016/S0002-9149(97)89177-1
10.1001/archinte.158.10.1074
Packer M. Do angiotensin-converting enzyme inhibitors prolong life in patients with heart failure treated in clinical practice? J Am Coll Cardiol 1996; 333:1670–1676.
10.1161/circ.61.5.6244906
10.1016/S0735-1097(83)80233-2
10.1016/0002-8703(88)90621-7
10.1093/eurheartj/12.6.705
10.1093/oxfordjournals.eurheartj.a015040
10.1016/S1388-9842(98)00002-6
10.1056/NEJM198706043162301
10.1056/NEJM199107253250427
10.1016/0002-9149(92)91394-J
10.2307/2336502
10.2307/2530245
10.1161/circ.90.5.7955203
10.1053/euhj.1997.0839

Dates

Type	When
Created	13 years, 2 months ago (June 11, 2012, 8:42 p.m.)
Deposited	1 year, 3 months ago (May 12, 2024, 9:01 a.m.)
Indexed	16 hours, 28 minutes ago (Aug. 29, 2025, 6:23 a.m.)
Issued	25 years, 8 months ago (Dec. 7, 1999)
Published	25 years, 8 months ago (Dec. 7, 1999)
Published Print	25 years, 8 months ago (Dec. 7, 1999)

Funders 0

None

BibTeX

@article{Packer_1999, title={Comparative Effects of Low and High Doses of the Angiotensin-Converting Enzyme Inhibitor, Lisinopril, on Morbidity and Mortality in Chronic Heart Failure}, volume={100}, ISSN={1524-4539}, url={http://dx.doi.org/10.1161/01.cir.100.23.2312}, DOI={10.1161/01.cir.100.23.2312}, number={23}, journal={Circulation}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Packer, Milton and Poole-Wilson, Philip A. and Armstrong, Paul W. and Cleland, John G. F. and Horowitz, John D. and Massie, Barry M. and Rydén, Lars and Thygesen, Kristian and Uretsky, Barry F.}, year={1999}, month=dec, pages={2312–2318} }

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  "abstract": "<jats:p>\n            <jats:italic>Background</jats:italic>\n            \u2014Angiotensin-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.\n          </jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results</jats:italic>\n            \u2014We randomly assigned 3164 patients with New York Heart Association class II to IV heart failure and an ejection fraction \u226430% 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 (\n            <jats:italic>P</jats:italic>\n            =0.128) but a significant 12% lower risk of death or hospitalization for any reason (\n            <jats:italic>P</jats:italic>\n            =0.002) and 24% fewer hospitalizations for heart failure (\n            <jats:italic>P</jats:italic>\n            =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.\n          </jats:p>\n          <jats:p>\n            <jats:italic>Conclusions</jats:italic>\n            \u2014These 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.\n          </jats:p>",
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