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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. [ABSTRACT FROM AUTHOR]

The aim of personalized medicine is to offer a tailored approach to each patient in order to provide the most effective therapy, while reducing risks and side effects. The use of mineralocorticoid receptor antagonists (MRAs) has demonstrated major benefits in heart failure with reduced ejection fraction (HFrEF), results with challenging inconsistencies in heart failure with preserved ejection fraction (HFpEF), and 'neutral' preliminary results in acute heart failure. Data derived from landmark trials are generally applied in a 'one size fits all' manner and the development and implementation of more personalized MRA management would offer the potential to improve outcomes and reduce side effects. However, the personalization of pharmacotherapy regimens remains poorly defined in the cardiovascular field (in light of current knowledge) and until further trials targeting specific subpopulations have been conducted, MRAs should be provided to the great majority of HFrEF patients in the absence of contraindication. Spironolactone should be considered for symptomatic HFpEF patients with elevated natriuretic peptides. In the near future, trials should target HFrEF patients using exclusion criteria sourced from landmark trials (e.g. severe renal impairment), select more homogeneous HFpEF populations (e.g. with elevated BNP and structural abnormalities on echocardiography), and determine which patients are likely to benefit from MRAs (e.g. according to prespecified biomarkers). [ABSTRACT FROM AUTHOR]