Table 2 RCTs evaluating SGLT2is in patients with HFrEF or worsening/acute HF (with or without T2DM)
Trial acronym | DAPA-HF | EMPEROR-Reduced | SOLOIST-WHF | CHIEF-HF | EMPULSE |
|---|---|---|---|---|---|
Trial name | Dapagliflozin and prevention of adverse outcomes in heart failure | Empagliflozin outcome trial in patients with chronic heart failure with reduced ejection fraction | Effect of sotagliflozin on cardiovascular events in participants with type 2 diabetes post worsening heart failure | A study on impact of canagliflozin on health status, quality of life, and functional status in heart failure | Empagliflozin in patients hospitalized with acute heart failure who have been stabilized |
Therapeutic area | HFrEF | HFrEF | HF (inpatient) | HF | HF (inpatient) |
ClinicalTrials.gov identifier | NCT03036124 | NCT03057977 | NCT03521934 | NCT04252287 | NCT04157751 |
ClinicalTrials.gov URL | |||||
Trial completion | Jul 2019 | May 2020 | Jun 2020 (terminated due loss of sponsor funding) | Nov 2021 | Jun 2021 |
Publication | McMurray et al., N Engl J Med 2019 [5] Jhund et al., Circl 2021 [102] | Packer et al., N Engl J Med 2020 [68] Zannad et al., Circl 2021 [92] | Bhatt et al., N Engl J Med 2021 [71] | Spertus et al., Nat Med 2022 [74] | Voors et al., Nat Med 2022 [75] |
Intervention (once daily) | Dapagliflozin 10 mg vs. PBO | Empagliflozin 10 mg vs. PBO | Sotagliflozin 200–400 mg vs. PBO | Canagliflozin 100 mg vs. PBO | Empagliflozin 10 mg vs. PBO |
LVEF eligibility |  ≤ 40% |  ≤ 40% | None (inpatient admission due to worsening HF regardless of EF) | None (> 40% and ≤ 40% eligible) | None (inpatient admission with acute HF regardless of EF) |
eGFR exclusion (mL/min/1.73 m2) |  < 30 |  < 20 or requiring dialysis |  < 30 |  < 30 or requiring dialysis |  < 20 or requiring dialysis |
Population | Randomized = 4744 (dapagliflozin, 2373; PBO, 2371) | Randomized = 3730 (empagliflozin, 1863; PBO, 1867) | Randomized = 1222 (sotagliflozin, 608; PBO, 614) | Randomized = 476 (ITT = 448: canagliflozin, 222; PBO, 226) | Randomized = 530 (empagliflozin, 265; PBO, 265) |
Trial duration | Median 18.2Â months | Median 16Â months | Median 9Â months | 12Â weeks | 90Â days |
Primary endpoint | Composite of worsening HF or CV death | Composite of CV death or HHF | Total number of CV deaths and hospitalizations and urgent HF visits | Change from baseline to week 12 in KCCQ-TSS | Hierarchical composite of death, HF events, time to first HF event, or ≥ 5-point change from baseline in KCCQ-TSS at 90 days |
Primary endpoint achieved? | Yes | Yes | Yes | Yes | Yes |
Details | 26% reduced risk of primary outcome with dapagliflozin (16.3% vs. 21.2% in PBO group; HR: 0.74, 95% CI 0.65–0.85; p < 0.001) | 25% reduced risk of primary outcome with empagliflozin (19.4% vs. 24.7% in PBO group; HR: 0.75, 95% CI 0.65–0.86; p < 0.001) | 33% reduced risk of primary outcome (events per 100 PY) with sotagliflozin (51.0 vs. 76.3 in PBO group; HR: 0.67, 95% CI 0.52–0.85; p < 0.001) | Mean 12-week change in KCCQ-TSS at week 12 was 4.3 points (95% CI 0.8–7.8; p = 0.016) in favor of canagliflozin | Win ratio 1.36 in favor of empagliflozin (53.89% wins vs. 39.71% wins in PBO group; 95% CI 1.09–1.68; p = 0.0054) |
Kidney endpoint | Secondary endpoint: Worsening kidney function (composite of sustained decline in eGFR ≥ 50%, ESKD [sustained eGFR < 15 mL/min/1.73 m2, long-term dialysis, or kidney transplantation], or renal death) | Secondary endpoint: Rate of decline from baseline in eGFR Other prespecified endpoint: Composite of chronic dialysis or renal transplant or sustained reduction from baseline in eGFR of ≥ 40%, or a sustained eGFR < 15 mL/min/1.73 m2 for patients with baseline eGFR ≥ 30 mL/min/1.73 m2, or a sustained eGFR < 10 mL/min/1.73 m2 for patients with baseline eGFR < 30 mL/min/1.73 m2 | Secondary endpoint (revised): Change in eGFR during follow-up | No kidney endpoints included | Occurrence of chronic dialysis or renal transplant or sustained reduction in eGFR from baseline ≥ 40% (eGFR < 15 mL/min/1.73 m2 for patients with baseline eGFR ≥ 30 mL/min/1.73 m2, sustained eGFR < 10 mL/min/1.73 m2 for patients with baseline eGFR < 30 mL/min/1.73 m2) |
Kidney endpoint achieved? | Composite-no; slowed eGFR decline-yes | Yes | No | Not applicable | No |
Details | Dapagliflozin 1.2% vs. PBO 1.6% (HR: 0.71, 95% CI 0.44–1.16; p = 0.17) From days 14–720: dapagliflozin –1.09 (95% CI –1.40 to −0.77) vs. PBO –2.85 (95% CI –3.17 to −2.53) mL/min/1.73 m2 per year; p < 0.001 | Empagliflozin slowed eGFR rate of decline vs. PBO (–0.55 vs.–2.28 mL/min/1.73 m2 per year [difference, 1.73]; 95% CI 1.10–2.37; p < 0.001) Empagliflozin reduced the frequency of the composite renal outcome: empagliflozin 1.6% vs. PBO 3.1% (HR: 0.50, 95% CI 0.32–0.77) | Change in eGFR favored PBO; sotagliflozin –0.34 vs. PBO –0.18 mL/min/1.73 m2 (difference –0.16; 95% CI –1.30 to 0.98; p value NA, as not included in hierarchical-testing strategy) |  | Not incorporated into model |