Systematic Review of Cardiovascular Benefits and Safety of Sacubitril-Valsartan in End-Stage Kidney Disease

Mariam Charkviani; Pajaree Krisanapan; Charat Thongprayoon; Iasmina M Craici; Wisit Cheungpasitporn

doi:10.1016/j.ekir.2023.10.008

Systematic Review of Cardiovascular Benefits and Safety of Sacubitril-Valsartan in End-Stage Kidney Disease

Kidney Int Rep. 2023 Oct 18;9(1):39-51. doi: 10.1016/j.ekir.2023.10.008. eCollection 2024 Jan.

Authors

Mariam Charkviani¹, Pajaree Krisanapan^{1

2}, Charat Thongprayoon¹, Iasmina M Craici¹, Wisit Cheungpasitporn¹

Affiliations

¹ Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
² Division of Nephrology, Department of Internal Medicine, Thammasat University Hospital, Pathum Thani, Thailand.

Abstract

Introduction: Patients with end-stage kidney disease (ESKD) frequently develop heart failure, contributing to high mortality. Limited data exist on cardiovascular benefits and safety of sacubitril-valsartan in this population. Our systematic review aims to evaluate the efficacy and safety of sacubitril-valsartan versus standard care in patients with ESKD who are on dialysis.

Methods: We conducted a search in Embase, MEDLINE, and Cochrane databases to identify relevant studies and assessed outcomes using random-effect model and generic inverse variance approach.

Results: Analysis of 12 studies involving 799 eligible patients with ESKD revealed improvement in left ventricular ejection fraction (LVEF) with sacubitril-valsartan compared to a control group with pooled mean difference (MD) 6.58% (95% confidence interval [CI]: 1.86, 11.29). LVEF significantly improved in patients with LVEF <50% (heart failure with reduced ejection fraction [HFrEF] and heart failure with moderately reduced ejection fraction [HFmrEF]) with MD 12.42% (95% CI: 9.39, 15.45). However, patients with LVEF >50% (heart failure with preserved ejection fraction [HFpEF]) did not exhibit statistically significant effect, MD 2.6% (95% CI: 1.15, 6.35). Sacubitril-valsartan significantly enhanced LVEF in patients with HFrEF, with MD 13.8% (95% CI: 12.04, 15.82). Safety analysis indicated no differences in incidence of hyperkalemia (pooled odds ratio [OR] 0.72; 95% CI: 0.38, 1.36) or hypotension (pooled risk ratio [RR] 1.03; 95% CI: 0.36, 2.98). No cases of angioedema were reported. However, safety analysis relies on evidence of limited robustness due to the observational nature of the studies.

Conclusion: Our systematic review suggests that sacubitril-valsartan benefits patients with ESKD with HFrEF and HFmrEF by improving LVEF without increasing the risk of hyperkalemia, hypotension, or angioedema compared to standard care. However, safety analysis based on observational studies inherently has limitations for establishing causal relationships.

Keywords: dialysis; end-stage kidney disease; heart failure; meta-analysis; sacubitril-valsartan; systematic review.