Efficacy of Modern Therapies for Heart Failure with Reduced Ejection Fraction in Specific Population Subgroups: A Systematic Review and Network Meta-Analysis

Introduction:The efficacy and safety of emerging therapiesfor heart failure with reduced ejection fraction (HFrEF) haveneverbeencomparedinspecific subgroups of patients.Methods:PubMed, Cochrane Registry, Web of Science,Scopus, and EMBASE libraries were used to extract data. Weused the following keywords: (heart failure with reducedejection fraction OR HFrEF) AND (treatment OR therapy) OR(cardiovascular death) OR (hospitalization for heart failure).We compared randomized clinical trials for HFrEF emergingtherapies focusing on the elderly (patients>65 years oldand>75 years old), chronic kidney disease (CKD) (estimatedglomerularfiltration rate (eGFR)<60 mL/min), patientswith diabetes mellitus (DM), coronary heart disease (CAD),New York Heart Association (NYHA) class III/IV, women,patients on sacubitril/valsartan (S/V). The primary outcomewas the efficacy composite endpoint of cardiovasculardeath (CVD) and HF hospitalization (HFH).Results:S/Vsignificantly reduced the primary outcome inpatients>65 years old (RR: 0.80; 95% CI: 0.68-0.94) and withCKD (RR: 0.79; 95% CI: 0.69-0.90); dapagliflozin in pa-tients>65 (RR: 0.72; 95% CI: 0.60-0.86) and>75 years old(RR: 0.68; 95% CI: 0.53-0.87), in those with CKD (RR: 0.72;95% CI: 0.59-0.88), DM (RR: 0.75; 95% CI: 0.63-0.89), andCAD (RR: 0.77; 95% CI: 0.65-0.92); empagliflozin inpatients>65 years old (RR: 0.78; 95% CI: 0.66-0.93), thosewith DM (RR: 0.72; 95% CI: 0.60-0.86), CAD (RR: 0.82; 95% CI:0.68-0.99), women (RR: 0.59; 95% CI: 0.44-0.79), and inpatients on S/V (RR: 0.64; 95% CI: 0.45-0.91); vericiguat inpatientswithCKD(RR:0.84;95%CI:0.73-0.97) and NYHAclass III/IV (RR: 0.87; 95% CI: 0.77-0.98); omecamtiv mecarbilin patients with CAD (RR: 0.90; 95% CI: 0.82-0.99) and NYHAIII/IV (RR: 0.88; 95% CI: 0.80-0.97).Conclusion:EmergingHFrEF therapies show a clinical benefit with the reduction of the primary composite endpoint of CVD and HFH, witheach drug being more effective in specificpatientpopulation.(c) 2024 The Author(s).Published by S. Karger AG, Basel