TY - JOUR
T1 - A hierarchical kidney outcome using win statistics in patients with heart failure from the DAPA-HF and DELIVER trials
AU - Kondo, Toru
AU - Jhund, Pardeep S.
AU - Gasparyan, Samvel B.
AU - Yang, Mingming
AU - Claggett, Brian L.
AU - McCausland, Finnian R.
AU - Tolomeo, Paolo
AU - Vadagunathan, Muthiah
AU - Heerspink, Hiddo J.L.
AU - Solomon, Scott D.
AU - McMurray, John J.V.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/5
Y1 - 2024/5
N2 - Win statistics offer a new approach to the analysis of outcomes in clinical trials, allowing the combination of time-to-event and longitudinal measurements and taking into account the clinical importance of the components of composite outcomes, as well as their relative timing. We examined this approach in a post hoc analysis of two trials that compared dapagliflozin to placebo in patients with heart failure and reduced ejection fraction (DAPA-HF) and mildly reduced or preserved ejection fraction (DELIVER). The effect of dapagliflozin on a hierarchical composite kidney outcome was assessed, including the following: (1) all-cause mortality; (2) end-stage kidney disease; (3) a decline in estimated glomerular filtration rate (eGFR) of ≥57%; (4) a decline in eGFR of ≥50%; (5) a decline in eGFR of ≥40%; and (6) participant-level eGFR slope. For this outcome, the win ratio was 1.10 (95% confidence interval (CI) = 1.06–1.15) in the combined dataset, 1.08 (95% CI = 1.01–1.16) in the DAPA-HF trial and 1.12 (95% CI = 1.05–1.18) in the DELIVER trial; that is, dapagliflozin was superior to placebo in both trials. The benefits of treatment were consistent in participants with and without baseline kidney disease, and with and without type 2 diabetes. In heart failure trials, win statistics may provide the statistical power to evaluate the effect of treatments on kidney as well as cardiovascular outcomes.
AB - Win statistics offer a new approach to the analysis of outcomes in clinical trials, allowing the combination of time-to-event and longitudinal measurements and taking into account the clinical importance of the components of composite outcomes, as well as their relative timing. We examined this approach in a post hoc analysis of two trials that compared dapagliflozin to placebo in patients with heart failure and reduced ejection fraction (DAPA-HF) and mildly reduced or preserved ejection fraction (DELIVER). The effect of dapagliflozin on a hierarchical composite kidney outcome was assessed, including the following: (1) all-cause mortality; (2) end-stage kidney disease; (3) a decline in estimated glomerular filtration rate (eGFR) of ≥57%; (4) a decline in eGFR of ≥50%; (5) a decline in eGFR of ≥40%; and (6) participant-level eGFR slope. For this outcome, the win ratio was 1.10 (95% confidence interval (CI) = 1.06–1.15) in the combined dataset, 1.08 (95% CI = 1.01–1.16) in the DAPA-HF trial and 1.12 (95% CI = 1.05–1.18) in the DELIVER trial; that is, dapagliflozin was superior to placebo in both trials. The benefits of treatment were consistent in participants with and without baseline kidney disease, and with and without type 2 diabetes. In heart failure trials, win statistics may provide the statistical power to evaluate the effect of treatments on kidney as well as cardiovascular outcomes.
UR - https://www.scopus.com/pages/publications/85192179518
U2 - 10.1038/s41591-024-02941-8
DO - 10.1038/s41591-024-02941-8
M3 - Article
AN - SCOPUS:85192179518
SN - 1078-8956
VL - 30
SP - 1432
EP - 1439
JO - Nature Medicine
JF - Nature Medicine
ER -