Efficacy of sodium glucose cotransporter 2 inhibitors for heart failure with preserved and mildly reduced ejection fraction: a systematic review and meta-analysis

Abstract

Background: SGLT2 inhibition has been a breakthrough approach in the treatment for heart failure. A recent guideline has recommended SGLT2i for the treatment of patients with HFrEF to reduce the risk of HF hospitalization and death, regardless of presence of type 2 diabetes (1). However, its benefit in HFpEF and HFmrEF have yet to be established. We evaluated the cardiovascular outcomes of SGLT2i for HFpEF and HFmrEF. Methods: Randomized controlled trials on SGLT2i versus placebo in heart failure patients with left ventricular ejection fraction of more than 40% reporting CV outcomes were searched using Pubmed, CENTRAL, and ScienceDirect. Primary outcome was the composite of hospitalization for heart failure or CV death. Secondary outcomes were the individual HHF, CV death, as well as all-cause mortality. Pooled hazard ratios with 95% confidence intervals were used as effect estimates using fixed-effects model. Results: Six studies were included with a total of 10.450 patients. In the combined HFmrEF and HFpEF population, there was a significant reduction in composite of cardiovascular death and heart failure hospitalization in the SGLT2i group (HR 0.79, 95% CI 0.71-0.88, p<0.0001) compared to placebo, driven by a significant reduction in heart failure hospitalization (HR 0.73, 95% CI 0.63-0.84, p< 0.00001). In the distinct HFpEF population, there was a significant reduction in composite of cardiovascular death and heart failure hospitalization in the SGLT2i group (HR 0.75, 95% CI 0.63-0.88, p = 0.0007) compared to placebo. Conclusion: SGLT2i provides significant risk reduction in HF hospitalization or CV death among patients with HFpEF compared to placebo.