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Comparing Sacubitril/Valsartan Against Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure: A Systematic Review and Network Meta-analysis

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Abstract

Background and Objective

In recent trials, sodium-glucose cotransporter 2 (SGLT2) inhibitors proved effective as treatment for heart failure. However, the relative efficacy of sacubitril/valsartan against SGLT2 inhibitor in patients with heart failure remains unknown. Hence, we performed a network meta-analysis to compare the effects of sacubitril/valsartan against SGLT2 inhibitors on cardiovascular outcomes in patients with heart failure.

Methods

Four electronic databases (PubMed, Embase, Cochrane, SCOPUS) were searched for randomised-controlled trials (RCTs) published from 1st January 2000 to 25th September 2021. Two additional systematic reviews were conducted for RCTs of enalapril and valsartan to establish a common comparator arm. Frequentist network meta-analysis models were utilised to summarise the studies.

Results

Twenty-five RCTs were included, comprising a combined cohort of 47,275 patients. Network meta-analysis demonstrated that compared to SGLT2 inhibitors, sacubitril/valsartan achieved a larger hazard rate reduction in the composite of heart failure hospitalisation and cardiovascular death (hazard ratio [HR]: 0.86; 95% CI 0.75–0.98), cardiovascular death (HR: 0.78; 95% CI 0.65–0.94), and a larger mean change in systolic blood pressure at 8 or more months (weighted mean difference [WMD]: − 7.08 mmHg; 95% CI − 8.28 to − 5.89). There were no significant differences in treatment effects across heart failure hospitalisation, all-cause mortality, diastolic blood pressure at 12 weeks, and systolic blood pressure at 2–4 months. In patients with heart failure with reduced ejection fraction, sacubitril/valsartan achieved a 20% hazard rate reduction for cardiovascular death compared to SGLT2 inhibitors.

Conclusions

In patients with heart failure, sacubitril/valsartan was demonstrated to be superior to SGLT2 inhibitors in the treatment effect for the composite of heart failure hospitalisation and cardiovascular death, cardiovascular death, and long-term blood pressure.

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Correspondence to Ching-Hui Sia.

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Funding

This work was supported by the National University of Singapore Yong Loo Lin School of Medicine’s Junior Academic Faculty Scheme to CS.

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All authors have no conflict of interest to declare.

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Data used for this study can be accessed upon reasonable request from the corresponding author.

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Authors’ contributions

YHT, YNT, CSYY, NLS, and CS designed the study and developed the study protocol and tools. YHT, YNT, CSYY, and JYAC were responsible for data collection. YHT, YNT, CSYY, NLS, and CS analysed data and wrote the manuscript. All authors contributed to the conceptualisation of the research questions, interpretation of the results, and manuscript writing. All authors read and approved the final manuscript.

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Teo, Y.N., Teo, Y.H., Syn, N.L. et al. Comparing Sacubitril/Valsartan Against Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure: A Systematic Review and Network Meta-analysis. Clin Drug Investig 42, 1–16 (2022). https://doi.org/10.1007/s40261-021-01098-3

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