Do SGLT2 inhibitors reduce mortality in heart failure with reduced ejection fraction?
In heart failure with reduced ejection fraction (HFrEF), SGLT2 inhibitors reduce both mortality and hospitalisation. DAPA-HF randomised 4,744 patients with LVEF <=40% to dapagliflozin or placebo and found a significant reduction in the composite of worsening heart failure or cardiovascular death, with a reduction in all-cause mortality [1].
EMPEROR-Reduced randomised 3,730 patients with LVEF <=40% to empagliflozin or placebo and reported a consistent reduction in the composite of cardiovascular death or heart-failure hospitalisation, driven substantially by fewer hospitalisations [2].
A prespecified meta-analysis of both trials (over 8,000 patients) confirmed reductions in all-cause death, cardiovascular death, and the composite renal endpoint, supporting a class effect. Benefit was consistent whether or not patients had type 2 diabetes [3], which is why these agents are now recommended as a pillar of HFrEF therapy rather than as glucose-lowering drugs alone.
- Trials enrolled patients already receiving guideline-directed medical therapy, so results reflect added benefit on top of existing treatment, not monotherapy.
- Patients with advanced kidney impairment below the trial eGFR thresholds were excluded, so benefit and safety in that group are less certain.
Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction
Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure
SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials
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