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

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Citation: European Journal of Heart Failure. 20(2):359-369, 2018 02.PMID: 28980368Institution: MedStar Heart & Vascular InstituteForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Enalapril/ad [Administration & Dosage] | *Heart Failure/dt [Drug Therapy] | *Stroke Volume/de [Drug Effects] | Angiotensin-Converting Enzyme Inhibitors/ad [Administration & Dosage] | Canada/ep [Epidemiology] | Cause of Death/td [Trends] | Dose-Response Relationship, Drug | Double-Blind Method | Europe/ep [Epidemiology] | Follow-Up Studies | Heart Failure/mo [Mortality] | Heart Failure/pp [Physiopathology] | Humans | Stroke Volume/ph [Physiology] | Survival Rate/td [Trends] | Treatment Outcome | United States/ep [Epidemiology]Year: 2018ISSN:
  • 1388-9842
Name of journal: European journal of heart failureAbstract: 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.CONCLUSION: In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses. Copyright (c) 2017 The Authors. European Journal of Heart Failure (c) 2017 European Society of Cardiology.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).All authors: Aban IB, Adamopoulos C, Ahmed A, Allman RM, Anker SD, Aronow WS, Arundel C, Bhatt DL, Blackman MR, Butler J, Deedwania P, Dooley DJ, Filippatos GS, Fletcher RD, Fonarow GC, Forman DE, Kanonidis IE, Lam PH, Patel K, Pitt B, White MFiscal year: FY2018Digital Object Identifier: Date added to catalog: 2017-10-17
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Journal Article MedStar Authors Catalog Article 28980368 Available 28980368

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.

CONCLUSION: In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses. Copyright (c) 2017 The Authors. European Journal of Heart Failure (c) 2017 European Society of Cardiology.

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).

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