Table 1 RCTs evaluating SGLT2is in patients with HFpEF (with or without T2DM)
Trial acronym | DELIVER | EMPEROR-Preserved | PRESERVED-HF | DETERMINE-Preserved | EMPERIAL-Preserved |
|---|---|---|---|---|---|
Trial name | Dapagliflozin evaluation to improve the lives of patients with preserved ejection fraction heart failure | Empagliflozin outcome trial in patients with chronic heart failure with preserved ejection fraction | Dapagliflozin in preserved ejection fraction heart failure | Dapagliflozin effect on exercise capacity using a 6-minute walk test in patients with heart failure with preserved ejection fraction | Effect of empagliflozin on exercise ability and HF symptoms in patients with chronic heart failure |
Therapeutic area | HFpEF | HFpEF | HFpEF | HFpEF | HFpEF |
Clinicaltrials.gov identifier | NCT03619213 | NCT03057951 | NCT03030235 | NCT03877224 | NCT03448406 |
ClinicalTrials.gov URL | |||||
Trial completion | Mar 2022 | Apr 2021 | Aug 2021 | Jul 2020 | Oct 2019 |
Publication | Solomon et al., N Engl J Med 2022 [59] McCausland et al., JAMA Cardiol 2022 [62] | Anker et al., N Engl J Med 2021 [61] | Nassif et al., Nat Med 2021 [72] | Unpublished; details from clinicaltrials.gov | Abraham et al., Eur Heart J 2021 [73] |
Intervention (once daily) | Dapagliflozin 10Â mg vs. PBO | Empagliflozin 10Â mg vs. PBO | Dapagliflozin 10Â mg vs. PBO | Dapagliflozin 10Â mg vs. PBO | Empagliflozin 10Â mg vs. PBO |
LVEF eligibility |  > 40% |  > 40% |  ≥ 45% |  > 40% |  > 40% |
eGFR exclusion (mL/min/1.73 m2) |  < 25 |  < 20 or requiring dialysis |  < 20 |  < 25 |  < 20 or requiring dialysis |
Population | Randomized = 6263 (dapagliflozin, 3131; PBO, 3132) | Randomized = 5988 (empagliflozin, 2997; PBO, 2991) | Randomized = 324 (dapagliflozin, 162; PBO, 162) | Randomized = 504 (dapagliflozin, 253; PBO, 251) | Randomized = 315 (empagliflozin, 157; PBO, 158) |
Trial duration | Median 2.3Â years | Median 26.2Â months | 12Â weeks | 16Â weeks | 12Â weeks |
Primary endpoint | Composite of worsening HF (unplanned HHF, or urgent HF visit) or CV death | Composite of CV death or HHF | Change from baseline to week 12 in KCCQ-CSS | Change from baseline to week 16 in KCCQ-TSS, KCCQ-PLS, and 6MWTD | Change from baseline to week 12 in 6MWTD |
Primary endpoint achieved? | Yes | Yes | Yes | No | No |
Details | 18% reduced risk of primary outcome with dapagliflozin (16.4% vs. 19.5% in PBO group; HR: 0.82, 95% CI 0.73–0.92; p < 0.001) Baseline kidney function did not affect primary composite CV outcome (eGFR ≥ 60 mL/min/1.73 m2: HR: 0.84, 95% CI 0.70–1.00; eGFR 45– < 60 mL/min/1.73 m2: HR: 0.68; 95% CI 0.54–0.87; eGFR < 45 mL/min/1.73 m2: HR: 0.93, 95% CI 0.76–1.14; p for interaction = 0.16) | 21% reduced risk of primary outcome with empagliflozin (13.8% vs. 17.1% in PBO group; HR: 0.79, 95% CI 0.69–0.90; p < 0.001) | Mean 12-week change in KCCQ-CS was 5.8 points (95% CI 2.3–9.2; p = 0.001) in favor of dapagliflozin | Dapagliflozin had no effect on the primary outcome measures; median difference dapagliflozin vs. PBO 3.16 (95% CI 0.36 to 6.01; p = 0.08) in KCCQ-TSS, 3.12 (95% CI –0.09 to 5.37; p = 0.23) in KCCQ-PLS, and 1.6 m (95% CI –5.9 to 9.0; p = 0.67) in 6MWTD | Empagliflozin had no effect on the primary outcome; median difference at week 12 empagliflozin vs. PBO 4.0 m (95% CI –5.0 to 13.0; p = 0.37) in 6MWTD |
Kidney endpoint | Exploratory analysis: effect of treatment on eGFR slope Post hoc analysis: (1) composite of first sustained ≥ 50% decline in eGFR from baseline; (2) development of ESKD (from AE reporting or sustained decline in eGFR < 15 mL/min/1.73 m2); or (3) death due to kidney causes | Secondary endpoint: rate of decline from baseline in eGFR Other prespecified endpoint: composite of chronic dialysis or renal transplant or sustained reduction from baselines in eGFR of ≥ 40% (< 15 mL/min/1.73 m2 for patients with baseline eGFR ≥ 30 mL/min/1.73 m2, or < 10 mL/min/1.73 m2 for patients with baseline eGFR < 30 mL/min/1.73 m2) (defined per clinicaltrials.gov entry) | No kidney endpoints included | No kidney endpoints included | No kidney endpoints included |
Kidney endpoint achieved? | Yes (exploratory endpoint only) | Yes (secondary endpoint only) | Not applicable | Not applicable | Not applicable |
Details | Dapagliflozin slowed rate of eGFR decline (from baseline to month 36: difference, + 0.5 [95% CI 0.1–0.9] mL/min/1.73 m2 per year; p = 0.01; and from months 1–36: difference, + 1.4 [95% CI 1.0–1.8] mL/min/1.73 m2 per year; p < 0.001) Dapagliflozin had no effect on frequency of composite kidney outcome: dapagliflozin 2.5% vs. PBO 2.3% (HR: 1.08, 95% CI 0.79–1.49) | Empagliflozin slowed eGFR rate of decline vs. PBO (–1.25 vs. –2.62 mL/min/1.73 m2 per year [difference, 1.36]; (95% CI 1.06–1.66; p < 0.001) Empagliflozin had no effect on frequency of composite kidney outcome: empagliflozin 3.6% vs. PBO 3.7% (HR: 0.95, 95% CI 0.73–1.24) |  |  |  |