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. 2022 Apr 14;12(4):989. doi: 10.3390/diagnostics12040989

Table 1.

SGLT-2i treatment outcome in primary HFrEF clinical trials.

HF Clinical Trial Study Population
Inclusion Criteria		 Major Outcome Measures Summary
DAPA-HF
Dapagliflozin: 10 mg or 5 mg tablets given once daily/up to 27.8 months.
McMurray et al.,
2019 [24]

  • HFrEF (LVEF ≤ 40%),

    with/without T2DM.

  • Sample size—4744

  • Male/female, ≥18 years

  • Symptomatic HFrEF (NYHA functional class II–IV), for ≥2 months

  • LVEF ≤ 40%

  • Elevated NT-proBNP Patients should receive background OMT for HFrEF according to locally recognized guidelines

  • eGFR ≥ 30 mL/min/1.73 m2 at

    enrolment

 Dapagliflozin vs. pacebo groups:

  • Composite of a first episode of worsening HF (hospitalization or an urgent visit resulting in IV therapy for HF) or CV death-event rate of 16.3% vs. 21.2%;

  • Composite of HHF or CV death-lower; (HR = 0.75, 0.65–0.85)

  • Total number of hospitalizations for HF and CV death-fewer (16.1% vs. 20.9%)

 Dapagliflozin reduced HHF and CV death
EMPEROR-REDUCED
Empagliflozin:
10 mg/once daily/up
to 1040 days
Packer et al.,
2020 [27]

  • Chronic HFrEF (LVEF ≤ 40%), irrespective of diabetes status.

  • Sample size—3730

  • Male/female, ≥18 years

  • EF ≥ 36% to ≤40%: NT-proBNP

    ≥ 500 pg/mL or patients without AF and NT-proBNP ≥ 5000 pg/mL for patients with AF

  • EF ≥ 31% to ≤35%: NT-proBNP

    ≥1000 pg/mL for patients without AF and NT-proBNP ≥ 2000 pg/mL for patients with AF

  • EF ≤ 30%: NT-proBNP ≥ 600 pg/mL for patients without AF and NT-proBNP ≥ 1200 pg/mL for patients with AF

  • EF ≤ 40% and hospitalization for HF in the past 12 months: NT-proBNP ≥ 600 pg/mL for patients without AF and NT-proBNP ≥ 1200 pg/mL for patients with AF

 Empagliflozin vs. placebo group:

  • Reduced hospitalization for worsening HF or CV death;

  • Overall combined risk was 25% lower in the empagliflozin group

  • The occurrence of all adjudicated hospitalizations for HF (first and recurrent events)—31% lower; Rate of decline in the eGFR was slower

 Empagliflozin reduced HHF and CV death; preserved renal function
EMPA-TROPISM
Empagliflozin: 10mg/once daily/6 months
Santos-Gallegos et al., 2021 [96]

  • HFrEF

  • Sample Size—84

  • Male/female, ≥18 years

  • Diagnosis of Heart failure (NYHA II to III)

  • LVEF < 50% on echocardiography

  • cMRI in the previous 6 months

  • Have stable symptoms and therapy for HF within the last 3 months.

 Empagliflozin vs. placebo group from baseline to 6 months:

  • LV end-systolic volume:

    26.6 mL vs. −0.5 mL (p < 0.001);

  • LV end-diastolic volume:

    25.1 vs. −1.5 mL (p < 0.001);

  • LVEF: 6.0% vs. −0.1% (p < 0.001);

  • LV mass: −17.8 g/m2 vs. 4.1 g/m2 (p < 0.001);

  • Peak VO2: 1.1 mL/kg/min vs. −0.5 mL/kg/min (p = 0.017);

  • 6-min walk test: 82 vs. −35 min (p < 0.001).

 Empagliflozin improved cardiac function (suggesting cardiac pressure overload improvement) and patient exercise capacity
EMPA-RESPONSE-AHF
Empagliflozin:
10 mg/daily/30 days
Damman et al.,
2020 [29]

  • Acute HF,

    Congestive HF with decompensation

  • Sample size—80

  • Male/female, ≥18 years

  • Hospitalized for AHF:
    • -
      Dyspnea at rest
    • -
      Signs of congestion, such as edema, rales, and/or congestion on chest radiograph
    • -
      BNP ≥ 350 pg/mL or NT-proBNP ≥ 1400 pg/mL
      (Patients with AF: BNP ≥ 500 pg/mL or NT-proBNP ≥ 2000 pg/mL)

  • Treated with loop diuretics

  • Able to be randomized within 24 h

  • Able and willing to provide freely given written informed consent

  • eGFR (CKD-EPI) ≥ 30 mL/min/1.73 m2

 Empagliflozin vs. placebo group:

  • No difference was observed in VAS dyspnea score, diuretic response, length of stay, or change in NT-proBNP;

  • Reduced a combined endpoint of in-hospital worsening HF, rehospitalization for HF or death at 60 days compared with placebo [4 (10%) vs. 13 (33%); p = 0.014];

  • Urinary output significantly greater [difference 3449 (95% confidence interval 578–6321) mL; p < 0.01];

  • No adverse effects on blood pressure or renal function.

 Empagliflozin reduced HHF; acute setting and small sample size limited results

Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure (DAPA-HF); Empagliflozin Outcome in Chronic Heart Failure with Reduced Ejection Fraction (EMPEROR-REDUCED); Are the “Cardiac Benefits” of Empagliflozin Independent of Its Hypoglycemic Activity? (EMPA-TROPISM); Effects of Empagliflozin on Clinical Outcomes in Patients with Acute Decompensated HF (EMPA-RESPONSE-AHF); Type 2 diabetes mellitus (T2DM); Atherosclerotic cardiovascular disease (ASCVD); Myocardial infarction (MI); Cardiovascular (CV); CV disease (CVD); Hospitalization for heart failure (HHF); Heart failure (HF); Left ventricular ejection fraction (LVEF); Heart failure with reduced ejection fraction (HFrEF); Left ventricular (LV); Estimated glomerular filtration rate (eGFR); End-stage renal disease (ESRD); Chronic kidney disease (CKD); Hazard ratio (HR); Atrial fibrillation (AF).