Trials of sodium-glucose cotransporter 2 inhibitors in heart failure
| Trial | Patients | Intervention | Primary composite end point | Primary composite results |
|---|---|---|---|---|
| Heart failure with reduced ejection fraction | ||||
| DAPA-HF (2019)8 | 4,744 adults EF ≤ 40% Established HF eGFR < 30 mL/minute/1.73 m2 | Dapagliflozin 10 mg | Cardiovascular death or worsening heart failure | 16.3% vs 21.2% (NNT = 21) |
| EMPEROR-Reduced (2020)9 | 3,730 adults EF ≤ 40% Established HF eGFR < 20 mL/minute/1.73 m2 | Empagliflozin 10 mg | Cardiovascular death or worsening heart failure | 19.4% vs 24.7% (NNT = 19) |
| Heart failure with preserved ejection fraction | ||||
| EMPEROR-Preserved (2021)15 | 5,988 adults EF > 40% New York Heart Association class II–IV HF eGFR < 20 mL/minute/1.73 m2 | Empagliflozin 10 mg | Cardiovascular death or hospitalization for heart failure | 13.8% vs 17.1% (NNT = 31) |
| DELIVER-HF (2022)16 | 6,263 adults EF > 40% Stabilized HF eGFR > 25 mL/minute/1.73 m2 With or without diabetes mellitus | Dapagliflozin 10 mg | Cardiovascular death or worsening heart failure | 16.4% vs 19.5% (NNT = 32) |
| Acute decompensated heart failure | ||||
| EMPULSE (2022)19 | 530 adults Any EF Acute decompensated HF eGFR < 20 mL/minute/1.73 m2 | Empagliflozin 10 mg | All-cause death, heart failure events,a Kansas City Cardiomyopathy Questionnaire score | 53.4% vs 39.7% Win ratiob 1.36 (95% confidence interval: 1.09–1.68) |
| SOLOIST-WHF (2021)20 | 1,222 adults Any EF Acute decompensated HF eGFR < 30 mL/minute/1.73 m2 Type 2 diabetes | Sotagliflozin 200 or 400 mg | Events of cardiovascular deaths, hospitalizations and urgent visits for heart failure | 51% vs 76.3% (NNT = 4) |
↵a EMPULSE: heart failure events include heart failure hospitalizations, urgent heart failure visit, unplanned outpatient heart failure visit, and worsening symptoms or intensification of therapy.
↵b Win ratio in favor of empagliflozin; the primary outcome analysis defined a “win” as when, in the common follow-up time, the patient did not die, have an increased number of exacerbations, have an earlier time to first exacerbation, or have a change in Kansas City Cardiomyopathy Questionnaire score < 5 points in hierarchal fashion. If any end point was achieved, it was considered a loss. The “wins ratio” was calculated for each group as the ratio of “wins” to “losses.”
DAPA-HF = Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure; DELIVER-HF = Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure; EF = ejection fraction; eGFR = estimated glomerular filtration rate; EMPEROR-Preserved = Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction; EMPEROR-Reduced = Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction; EMPULSE = Empagliflozin in Patients Hospitalized With Acute Heart Failure Who Have Been Stabilized; HF = heart failure; NNT = number needed to treat; SOLOIST-WHF = Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure