From:  Reframing SGLT2 inhibition as systematic metabolic stress modulation across the cardiovascular-renal-metabolic axis

 Summary of major randomized controlled trials evaluating cardiovascular outcomes of SGLT2 inhibitors across HF phenotypes.

TrialDrugPopulationEF rangeSample sizePrimary outcomeKey resultsMortality benefit
DAPA-HFDapagliflozinSymptomatic HFrEF with or without T2DM≤ 40%4,744Composite of CV death or worsening HF26% relative risk reduction in primary outcomeReduced CV death and HF hospitalization
EMPEROR-ReducedEmpagliflozinChronic HFrEF≤ 40%3,730CV death or HF hospitalization25% reduction in primary composite endpointTrend toward reduced CV mortality
EMPEROR-PreservedEmpagliflozinHFpEF> 40%5,988CV death or HF hospitalization21% reduction driven mainly by reduced HF hospitalizationNo significant mortality reduction
DELIVERDapagliflozinHFmrEF and HFpEF> 40%6,263CV death or worsening HF18% reduction in primary composite outcomeModest mortality effect
EMPULSEEmpagliflozinAcute decompensated HF (hospitalized patients)All EF ranges530Composite clinical benefit at 90 daysImproved clinical status and reduced rehospitalizationNot powered for mortality
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Differences in inclusion criteria (e.g., EF thresholds, natriuretic peptide levels, renal function) and baseline characteristics across trials should be considered when comparing outcomes across HF phenotypes. CV: cardiovascular; T2DM: type 2 diabetes mellitus; HFrEF: heart failure with reduced ejection fraction; HFpEF: heart failure with preserved ejection fraction; HFmrEF: heart failure with mildly reduced ejection fraction.