1. Similar clinical benefits from below‐target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial
- Author
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Lam, Phillip H, Dooley, Daniel J, Fonarow, Gregg C, Butler, Javed, Bhatt, Deepak L, Filippatos, Gerasimos S, Deedwania, Prakash, Forman, Daniel E, White, Michel, Fletcher, Ross D, Arundel, Cherinne, Blackman, Marc R, Adamopoulos, Chris, Kanonidis, Ioannis E, Aban, Inmaculada B, Patel, Kanan, Aronow, Wilbert S, Allman, Richard M, Anker, Stefan D, Pitt, Bertram, and Ahmed, Ali
- Subjects
Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Clinical Sciences ,Cardiovascular ,Clinical Research ,Clinical Trials and Supportive Activities ,Heart Disease ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Good Health and Well Being ,Angiotensin-Converting Enzyme Inhibitors ,Canada ,Cause of Death ,Dose-Response Relationship ,Drug ,Double-Blind Method ,Enalapril ,Europe ,Follow-Up Studies ,Heart Failure ,Humans ,Stroke Volume ,Survival Rate ,Treatment Outcome ,United States ,ACE inhibitors ,Target dose ,Placebo ,Heart failure ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
AimsTo 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 resultsTwo 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).ConclusionIn patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses.
- Published
- 2018