Cardiorenal effects of SGLT2i in combination with ARNI for HFrEF: a systematic review and meta-analysis

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Background Recent recommendations suggest a combination of Angiotensin receptor neprilysin inhibitor (ARNI) and beta blocker with other classes of medications in heart failure with reduced ejection fraction (HFrEF) (1). Despite currently available treatment options, mortality remains high (2). From the recent robust clinical trials, both SGLT2 inhibitor (SGLT2i) and ARNI have been found to decrease HF hospitalizations and CV death (3-5). This paper aims to determine the efficacy of SGLT2i and ARNI combination versus ARNI alone in the management of HFrEF. Methods Randomized controlled, prospective or retrospective cohort trials on ARNI with SGLT2i versus ARNI without SGLT2i in patients with left ventricular ejection fraction of 40% or less were included. A search using Pubmed, CENTRAL, and ScienceDirect was conducted on April 29, 2021. Risk of bias was assessed using Cochrane’s Collaboration tool for RCTs and STROBE checklist for cohort, case-control and cross-sectional studies. Review Manager version 5.4 software was used for data synthesis and analysis. Outcomes were measured as mean differences and risk ratio for continuous data and dichotomous data with 95% confidence interval. Results Three studies were screened with a total of 1,742 patients; 759 received a combination of SGLT2i and ARNI while 983 received standard care plus ARNI. There was a significant reduction in composite of cardiovascular death and heart failure hospitalization in the combination SGLT2i/ARNI group (HR 0.69, 95% CI 0.56-0.85, and p value of 0.0005). There was significant reduction in heart failure hospitalization in the treatment group with SGLT2i (HR of 0.61, a 95% CI 0.49-0.78) compared to the group without treatment of a SGLT2 inhibitor (< 0.0001). Composite renal event favors combination of ARNI and SGLT2i in some studies (HR of 0.73, with a 95% CI 0.39-1.38), however was not statistically significant (p value = 0.34). Conclusion Addition of SGLT2i with ARNI provides significant decrease in mortality and hospitalization among patients with HFrEF compared to control as well as improvement in renal function.