Summary

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• This summary is based on the review of 30 systematic review(s)/meta-analysis(es). ^[1-30]
• Heart Failure with Reduced Ejection Fraction (HFrEF): Sacubitril/valsartan (S/V) significantly reduced the combined risk of cardiovascular death and heart failure hospitalization (HFH) in patients over 65 years old (risk ratio (RR): 0.80; 95% confidence interval (CI) 0.68-0.94) and those with chronic kidney disease (CKD), with additional improvements noted in left ventricular ejection fraction (LVEF) (mean difference (MD): 13.8%; 95% CI 12.04-15.82) and health-related quality of life (HRQoL).
• Heart Failure with Preserved Ejection Fraction (HFpEF) and Mildly Reduced Ejection Fraction (HFmrEF): S/V demonstrated superior outcomes in HFpEF and HFmrEF compared to valsartan, enhancing Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary scores (CSS), NYHA (New York Heart Association) class (odds ratio (OR): 1.32), and reducing the composite endpoint of HFH and cardiovascular death (RR: 0.86); additionally, S/V lowered N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, delayed renal function deterioration, and reduced HF hospitalizations.
• Comparative Effectiveness with Other Drugs: S/V was favorable compared to traditional renin-angiotensin-aldosterone system (RAAS) inhibitors, while sodium-glucose cotransporter-2 (SGLT2) inhibitors showed superior reductions in HF hospitalizations specifically in HFpEF patients. Vericiguat demonstrated non-inferior effects to S/V for cardiovascular death and HFH in broader heart failure populations.
• General Safety and Adverse Effects: Sacubitril/valsartan (S/V) showed an increased risk of hypotension compared to valsartan (OR 1.67, 95% CI 1.27-2.19) and ACE inhibitors/ARBs (RR 1.69, 95% CI 1.33-2.15), with no significant increase in hyperkalemia or angioedema risks compared to control groups.
• Safety in Specific Populations: In patients with CKD, S/V was effective in preventing serum creatinine elevation and estimated glomerular filtration rate (eGFR) decline, without increasing the risk of hyperkalemia or hypotension. Similarly, patients with end-stage kidney disease (ESKD) did not show significant increases in hypotension or hyperkalemia risk when treated with S/V.
• Elderly patients (>65 and >75 years), CKD patients (eGFR < 60 ml/min), and patients with New York Heart Association (NYHA) Class III/Intravenous (IV) heart failure all demonstrated clinically significant cardiovascular improvements with sacubitril/valsartan, including reductions in cardiovascular death, heart failure hospitalizations, and renal function preservation. Similarly, patients with CKD stages 3-5 experienced reduced cardiovascular events and maintained renal function, while those on dialysis showed improved LVEF without notable safety issues.