학술논문

Similar clinical benefits from below‐target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial
Document Type
article
Source
European Journal of Heart Failure. 20(2)
Subject
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
Language
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.