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

Pubmed ID: 28980368

Pubmed Central ID: PMC6500736

Journal: European journal of heart failure

Publication Date: Feb. 1, 2018

MeSH Terms: Humans, United States, Heart Failure, Treatment Outcome, Cause of Death, Follow-Up Studies, Angiotensin-Converting Enzyme Inhibitors, Survival Rate, Stroke Volume, Double-Blind Method, Europe, Dose-Response Relationship, Drug, Canada, Enalapril

Grants: R01 HL085561, R01 HL097047, P30 AG024827, UL1 TR001409

Authors: White M, Aronow WS, Ahmed A, Adamopoulos C, Filippatos GS, Anker SD, Butler J, Fonarow GC, Aban IB, Deedwania P, Pitt B, Allman RM, Patel K, Fletcher RD, Forman DE, Blackman MR, Lam PH, Dooley DJ, Bhatt DL, Arundel C, Kanonidis IE

Cite As: Lam PH, Dooley DJ, Fonarow GC, Butler J, Bhatt DL, Filippatos GS, Deedwania P, Forman DE, White M, Fletcher RD, Arundel C, Blackman MR, Adamopoulos C, Kanonidis IE, Aban IB, Patel K, Aronow WS, Allman RM, Anker SD, Pitt B, Ahmed A. Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial. Eur J Heart Fail 2018 Feb;20(2):359-369. Epub 2017 Oct 5.

Studies:

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.