SGLT2 Inhibitors in Heart Failure: Living Meta-Analysis Across the EF Spectrum

Abstract

In patients with heart failure across the full ejection fraction spectrum, do SGLT2 inhibitors cause a reduction in cardiovascular death or heart failure hospitalisation? 21,947 patients with HFrEF, HFmrEF, or HFpEF were registered into five randomised placebo-controlled trials to compare dapagliflozin or empagliflozin against placebo over follow ups of median 16 to 27 months. A DerSimonian-Laird random-effects meta-analysis collected hazard ratios on the log scale with HKSJ adjustment. There was no evident heterogeneity (I-squared 0%) across EF strata, with the collected hazard ratio being 0.77 (95% CI 0.72-0.82). Diabetes status, baseline diuretic use and natriuretic peptide levels had no impact on subgroup analysis which showed consistent benefit. There is a 23% relative reduction in cardiovascular events across the heart failure spectrum due to SGLT2 inhibitors which supports consolidating them in all four pillars of HF guideline-directed treatment as integral therapy. However, evidence for canagliflozin through class-effect generalisability in HF remains less established and genitourinary infections are more common along with supervising mycotic infections.