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Eur J Heart Fail. 2018 Feb;20(2):359-369. doi: 10.1002/ejhf.937. Epub 2017 Oct 5.

Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial.

Author information

1
Veterans Affairs Medical Center, Washington, DC, USA.
2
Georgetown University/MedStar Washington Hospital Center, Washington, DC, USA.
3
University of California, Los Angeles, CA, USA.
4
Stony Brook University, Stony Brook, NY, USA.
5
Brigham and Women's Hospital Heart and Vascular Center, Boston, MA, USA.
6
Attikon University Hospital, Athens, Greece.
7
University of California, San Francisco, Fresno, CA, USA.
8
University of Pittsburgh and VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
9
Université de Montréal, Montreal, Canada.
10
Georgetown University, Washington, DC, USA.
11
George Washington University, Washington, DC, USA.
12
St Paul General Hospital, Thessaloniki, Greece.
13
Hippocration Hospital, Thessaloniki, Greece.
14
University of Alabama at Birmingham, Birmingham, AL, USA.
15
University of California, San Francisco, CA, USA.
16
Westchester Medical Center and New York Medical College, Valhalla, NY, USA.
17
Department of Veterans Affairs, Geriatrics and Extended Care, Washington, DC, USA.
18
Division of Cardiology and Metabolism - Heart Failure, Cachexia and Sarcopenia, Department of Cardiology (CVK); and Berlin-Brandenburg Center for Regenerative Therapies (BCRT); Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) Berlin, Charité Universitätsmedizin Berlin, Germany.
19
Department of Cardiology and Pneumology, University Medicine Göttingen, Germany.
20
University of Michigan, Ann Arbor, MI, USA.

Abstract

AIMS:

To examine associations of below-target and target dose of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, with outcomes in patients with heart failure and reduced ejection fraction (HFrEF) in the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial.

METHODS AND RESULTS:

Two thousand five hundred and sixty-nine patients with HFrEF (ejection fraction ≤35%) were randomized to below-target (5-10 mg/day) dose placebo (n = 1284) or enalapril (n = 1285). One month post-randomization, blind up-titration to target (20 mg/day) dose was attempted for both study drugs in 2458 patients. Among the 1444 patients who achieved dose up-titration (placebo, n = 748; enalapril, n = 696; mean dose for both groups, 20.0 mg/day), target dose enalapril (vs. target dose placebo) was associated with a 9% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality [adjusted hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.60-0.81; P < 0.001] during 4 years of follow-up. Among the 1014 patients who could not achieve target dose (placebo, n = 486; enalapril, n = 528; mean dose for both groups, 8.8 mg/day), below-target dose enalapril (vs. below-target dose placebo) was associated with a 12% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 0.68; 95% CI 0.57-0.81; P < 0.001). Among the 1224 patients receiving enalapril, target (vs. below-target) dose had no association with the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 1.04; 95% CI 0.87-1.23; P = 0.695).

CONCLUSION:

In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses.

KEYWORDS:

ACE inhibitors; Enalapril; Heart failure; Placebo; Target dose

PMID:
28980368
PMCID:
PMC6500736
DOI:
10.1002/ejhf.937
[Indexed for MEDLINE]
Free PMC Article

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