Which Sodium-Glucose Cotransporter 2 Inhibitors Agent is More Effective in Patients With Heart Failure? A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials

Background: Treatment with various sodium-glucose cotransporter 2 inhibitors (SGLT-2Is) has decreased cardiovascular events in patients with heart failure (HF). Therefore, we conducted a network meta-analysis to investigate which SGLT-2Is are more effective in patients with HF. Methods: PubMed, Web of Science, Scopus, and Embase, were systematically searched from inception to February 2022. We included randomized controlled trials (RCTs) that investigated the use of SGLT-2Is vs. placebo in HF patients. The main outcomes were all-cause, cardiovascular mortality, serious adverse events, and hospitalizations due to HF. The random-effects method model and inverse variance statistics were used to calculate the odds ratio (OR) with a 95% confidence interval (CI). Results: Our study included 12 RCTs with a total number of 69,024 patients (37,923 in the SGLT2 inhibitors group and 31,101 in the placebo group). Five RCTs used empagliflozin, 4 used dapagliflozin, 1 used canagliflozin, 1 used ertugliflozin, and 1 used sotagliflozin. Our analysis showed that empagliflozin has a statistically significant lowest odds for both cardiovascular mortality and serious adverse effects (OR: 0.80 with 95% CI [0.67-0.96]) and (OR: 0.84 with 95% CI [0.76-0.93]), respectively compared to other SGLT-2Is. All SGLT-2Is have been associated with the same lower odds without preferences for one over the others regarding all-cause mortality. Furthermore, the hospitalization rate due to HF showed a statistically significant decrease with all the SGLT-2Is except for canagliflozin, which showed insignificant results with (OR: 0.63 with 95% CI [0.39-1.01]). Conclusion: No differences between the SGLT-2Is included in this analysis were observed in terms of all-cause mortality. Empagliflozin had the lowest odds of cardiovascular mortality and serious adverse effects. Canagliflozin was the only SGLT-2Is that showed no significant results in odds of hospitalization for HF.