Clin Drug Investig. 2022 Jan;42(1):1-16. doi: 10.1007/s40261-021-01098-3. Epub 2021 Nov 19.

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

Clinical drug investigation

Yao Neng Teo, Yao Hao Teo, Nicholas L Syn, Celine Shuen Yin Yoong, Alex Jia Yang Cheong, Caitlin Fern Wee, Yoke-Ching Lim, Chi-Hang Lee, Tiong-Cheng Yeo, Ping Chai, Raymond C C Wong, Weiqin Lin, Ching-Hui Sia

PMID: 34797518 DOI: 10.1007/s40261-021-01098-3

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.

© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

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