Abstract: SA-PO886
Consistent Benefits of Dapagliflozin on Kidney End Points Defined by Different eGFR Thresholds: A Prespecified Analysis From DAPA-CKD
Session Information
- CKD: Clinical Trials and Pharmacoepidemiology
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2202 CKD (Non-Dialysis): Clinical‚ Outcomes‚ and Trials
Authors
- Jongs, Niels, Universiteit Groningen Faculteit Medische Wetenschappen, Groningen, Groningen, Netherlands
- Chertow, Glenn, Stanford University School of Medicine, Stanford, California, United States
- McMurray, John, University of Glasgow, Glasgow, Glasgow, United Kingdom
- Correa-Rotter, Ricardo, National Medical Science and Nutrition Institute Salvador Zubiran, Mexico City, Mexico
- Rossing, Peter, Steno Diabetes Center Copenhagen, Herlev, Capital Region, Denmark
- Langkilde, Anna Maria, AstraZeneca, BioPharmaceuticals R&D, Gothenburg, Sweden
- Sjostrom, David, AstraZeneca, BioPharmaceuticals R&D, Gothenburg, Sweden
- Toto, Robert D., UT Southwestern Medical Center, Department of Internal Medicine, Dallas, Texas, United States
- Wheeler, David C., University College London Faculty of Medical Sciences, London, London, United Kingdom
- L Heerspink, Hiddo Jan, Universiteit Groningen Faculteit Medische Wetenschappen, Groningen, Groningen, Netherlands
Background
Doubling of serum creatinine (equivalent to 57% eGFR decline) is an accepted component of composite kidney endpoints. Recently, lesser eGFR declines (40%, 50%) have been used as alternative endpoint components. We assessed the effect of dapagliflozin on kidney endpoints using different eGFR decline to explore whether alternative eGFR thresholds are useful.
Methods
This post hoc analysis of DAPA-CKD (N=4304) compared the effect of dapagliflozin vs placebo on kidney outcomes, including different eGFR thresholds (≥57%, ≥50%, ≥40% eGFR decline from baseline), and a composite with end-stage kidney disease (ESKD) and kidney death. We used Cox-proportional hazards model adjusted for baseline eGFR and stratified according to randomization factors (type 2 diabetes; UACR ≤1000/>1000 mg/g).
Results
Over 2.4 years’ median follow-up, there were 201 (4.7%), 313 (7.3%) and 538 (12.5%) events of eGFR decline based on ≥57%, ≥50%, or ≥40% eGFR decline, respectively. Compared to the effect of dapagliflozin in reducing risk of ESKD and kidney death, effect sizes for dapagliflozin on eGFR endpoints, defined by ≥57%, ≥50%, or ≥40% decline, were comparable (Figure). Results were also similar when using eGFR endpoints or a composite with ESKD and kidney death (Figure) and in patients with or without type 2 diabetes.
Conclusion
Smaller declines in eGFR (≥40% and ≥50%) occurred more frequently than 57% decline and provided similar estimates of the efficacy of dapagliflozin on kidney outcomes. Use of smaller eGFR declines as endpoints may facilitate trials assessing CKD progression when sample size is limited.
Funding
- Commercial Support –