Secondary analysis
Endothelin-1, Outcomes in Patients With Heart Failure and Reduced Ejection Fraction, and Effects of Dapagliflozin: Findings From DAPA-HF
- Secondary analysis of the DAPA-HF randomised trial
Authors' conclusion
Higher baseline ET-1 concentration was independently associated with worse clinical outcomes and more rapid decline in kidney function. The benefit of dapagliflozin was consistent across the range of ET-1 concentrations measured, and treatment with dapagliflozin led to a small decrease in serum ET-1 concentration.
Study context
- Population
- Patients with HFrEF in DAPA-HF with baseline ET-1 measurements
- Participants
- 3,048 patients
- Comparison
- Outcomes by baseline ET-1 tertile; dapagliflozin vs placebo by ET-1 level
- T1n = 1,016reference
- T2n = 1,022
- T3n = 1,010
- Primary endpoint
- CV death or worsening HF
Primary result
As reported in the abstract
CV death or worsening HF, by baseline ET-1
Each group vs T1Adjusted hazard ratio (95% CI)
T3
1.95(1.53–2.50)
T2
1.36(1.06–1.75)
Further findings
mL/min per 1.73 m² per y
| Outcome | T1 | T2 | T3 | placebo-corrected decrease (pg/mL) (95% CI) | P value |
|---|---|---|---|---|---|
| eGFR slope by ET-1 tertile | −2.35 (95% CI −2.79–-1.91) | −2.08 (95% CI −2.52–-1.63) | −3.19 (95% CI −3.66–-2.72) | ||
| Change in ET-1 with dapagliflozin (placebo-corrected decrease) | 0.13 (0.25–0.01) | P = 0.029 |
- eGFR slope by ET-1 tertile: P=0.002
Dapagliflozin benefit by baseline ET-1
- Benefit of dapagliflozin consistent regardless of baseline ET-1
Original publication
Endothelin-1, Outcomes in Patients With Heart Failure and Reduced Ejection Fraction, and Effects of Dapagliflozin: Findings From DAPA-HF. Circulation. Published 11 April 2023. doi:10.1161/circulationaha.122.063327
Summarised from the published abstract; every number is checked against it