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 therapies for heart failure with reduced ejection fraction (HFrEF) have never been compared in specific subgroups of patients. Methods: Pubmed, Cochrane Registry, Web of Science, Scopus and EMBASE libraries were used to extract data. We used the following keywords: (heart failure with reduced ejection fraction OR HFrEF) AND (treatment OR therapy) OR (cardiovascular death) OR (hospitalization for heart failure). We compared randomized clinical trials (RCTs) for HFrEF emerging therapies focusing on elderly (patients > 65 years old and > 75 years old), chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) < 60 ml/min), diabetic patients, ischemic patients, New York Heart Association (NYHA) class III/IV, female sex, patients on sacubitril/valsartan (S/V). The primary outcome was the efficacy composite endpoint of cardiovascular death (CVD) and HF hospitalization (HFH). Results: S/V significantly reduced the primary outcome in patients > 65 years old (RR: 0.80; 95%CI: 0.68-0.94) and with CKD (RR: 0.79; 95%CI: 0.69-0.90); dapagliflozin in patients >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), diabetic (RR: 0.75; 95%CI: 0.63-0.89) and ischemic patients (RR: 0.77; 95%CI: 0.65-0.92); empagliflozin in patients >65 years old (RR: 0.78; 95%CI: 0.66-0.93), diabetic (RR: 0.72; 95%CI: 0.60-0.86), ischemic (RR: 0.82; 95%CI: 0.68-0.99), female sex (RR: 0.59; 95%CI: 0.44-0.79) and in patients on S/V (RR: 0.64; 95%CI: 0.45-0.91); vericiguat in patients with CKD (RR: 0.84; 95%CI: 0.73-0.97) and NYHA class III/IV (RR: 0.87; 95%CI: 0.77-0.98); OM in ischemic (RR: 0.90; 95%CI:0.82-0.99) and NYHA III/IV (RR: 0.88; 95%CI: 0.80-0.97) patients. Conclusion: Emerging HFrEF therapies show a clinical benefit with the reduction of the primary composite endpoint of CVD and HFH, with each drug being more effective in specific patient population.