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

Phillip H. Lam, Daniel J. Dooley, Gregg C. Fonarow, Javed Butler, Deepak L. Bhatt, Gerasimos S. Filippatos, Prakash Deedwania, Daniel E. Forman, Michel White, Ross D. Fletcher, Cherinne Arundel, Marc R. Blackman, Chris Adamopoulos, Ioannis E. Kanonidis, Inmaculada B. Aban, Kanan Patel, Wilbert S. Aronow, Richard M. Allman, Stefan D. Anker, Bertram PittAli Ahmed

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)359-369
Number of pages11
JournalEuropean Journal of Heart Failure
Volume20
Issue number2
DOIs
StatePublished - Feb 1 2018
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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