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

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.