Key result
Sacubitril/valsartan reduces major events ~20% in HFrEF patients over 65 years old.
Why the study?
The efficacy and safety of emerging therapies for HFrEF had never been compared in specific patient subgroups.
Do emerging HFrEF therapies reduce cardiovascular death and heart failure hospitalization in specific subgroups of patients with HFrEF?
Meta-Analysis
Do emerging HFrEF therapies reduce cardiovascular death and heart failure hospitalization in specific subgroups of patients with HFrEF?
Emerging HFrEF therapies show clinical benefit in reducing cardiovascular death and heart failure hospitalization, with varying efficacy profiles across specific patient subgroups.
May support targeted sacubitril/valsartan use in older HFrEF patients with CKD; extends meta-analytic evidence to key subgroups.
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 for HFrEF emerging therapies focusing on the elderly (patients >65 years old and >75 years old), chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) < 60 mL/min), patients with diabetes mellitus (DM), coronary heart disease (CAD), New York Heart Association (NYHA) class III/IV, women, 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), DM (RR: 0.75; 95% CI: 0.63-0.89), and CAD (RR: 0.77; 95% CI: 0.65-0.92); empagliflozin in patients >65 years old (RR: 0.78; 95% CI: 0.66-0.93), those with 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 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); omecamtiv mecarbil in patients with CAD (RR: 0.90; 95% CI: 0.82-0.99) and NYHA III/IV (RR: 0.88; 95% CI: 0.80-0.97). 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.
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Lavalle et al. (2024) conducted a meta-analysis in Heart failure with reduced ejection fraction (HFrEF). Emerging HFrEF therapies (sacubitril/valsartan, dapagliflozin, empagliflozin, vericiguat, omecamtiv mecarbil) was evaluated on Composite endpoint of cardiovascular death (CVD) and HF hospitalization (HFH). Emerging therapies for HFrEF reduced cardiovascular death and heart failure hospitalization in specific subgroups, such as sacubitril/valsartan in patients >65 years old (RR 0.80; 95% CI 0.68-0.94).
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