Kidney Week

Abstract: FR-OR58

Effects of Dapagliflozin on Kidney Function, Cardiovascular Events, and All-Cause Mortality According to Cause of Kidney Disease in the DAPA-CKD Trial

Session Information

• High-Impact Clinical Trials
  October 23, 2020 | Location: Live-Streamed
  Abstract Time: 12:15 PM - 12:30 PM

Category: CKD (Non-Dialysis)

• 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Wheeler, David C., The George Institute for Global Health, Sydney, Australia

David C. Wheeler, MD

• Stefansson, Bergur V., AstraZeneca, Gothenburg, Sweden

Bergur V. Stefansson,

• Correa-Rotter, Ricardo, National Medical Science and Nutrition Institute Salvador Zubirán, Mexico City, Mexico

Ricardo Correa-Rotter,

• Chertow, Glenn Matthew, Stanford University School of Medicine, Stanford, California, United States

Glenn Matthew Chertow,

• Greene, Tom, University of Utah Health Sciences, Salt Lake City, Utah, United States

Tom Greene,

• Hou, Fan Fan, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China

Fan Fan Hou,

• Jongs, Niels, University of Groningen, Groningen, Netherlands

Niels Jongs,

• McMurray, John, University of Glasgow Institute of Cardiovascular and Medical Sciences, Glasgow, Glasgow, United Kingdom

John McMurray,

• Rossing, Peter, Steno Diabetes Center, Copenhagen, Denmark

Peter Rossing,

• Sjostrom, David, AstraZeneca, Gothenburg, Sweden

David Sjostrom,

• Toto, Robert D., UT Southwestern Medical Center, Dallas, Texas, United States

Robert D. Toto,

• Langkilde, Anna Maria, AstraZeneca, Gothenburg, Sweden

Anna Maria Langkilde,

• L Heerspink, Hiddo Jan, The George Institute for Global Health, Sydney, Australia

Hiddo Jan L Heerspink,

Group or Team Name

• DAPA-CKD Investigators

Background

The Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease trial (DAPA-CKD) assessed the sodium glucose co-transporter 2 inhibitor dapagliflozin in patients with chronic kidney disease (CKD) with and without type 2 diabetes. This pre-specified analysis explores outcomes according to underlying cause of kidney disease.

Methods

4304 participants with eGFR 25–75 mL/min/1.73m² and UACR 200–5000 mg/g were randomized to receive dapagliflozin 10mg once daily or placebo. The effects of dapagliflozin versus placebo on the primary outcome (composite of sustained decline in eGFR ≥50%, end-stage kidney disease, or death from cardiovascular [CV] or kidney causes) and secondary outcomes (CV death or heart failure hospitalizations and all-cause mortality) were assessed in patients with diabetic nephropathy (n=2510), chronic glomerulonephritides (n=695), ischemic/hypertensive CKD (n=687) and CKD due to unknown/other causes (n=412).

Results

The effect of dapagliflozin on the primary outcome (hazard ratio [HR] 0.61, 95% Confidence Interval [CI] 0.51–0.72) was consistent in patients with diabetic nephropathy (HR 0.63, 95%CI 0.51–0.78), glomerulonephritides (HR 0.43, 95%CI 0.26–0.71), ischemic/hypertensive CKD (HR 0.75, 95%CI 0.44–1.26) and CKD of other/unknown cause (HR 0.58, 95%CI 0.29–1.19; p-interaction 0.53). The reduction in CV death or heart failure hospitalizations (HR 0.71, 95%CI 0.55–0.92) was also similar across kidney disease etiologies (p-interaction 0.24) as was reduction in all-cause mortality (HR 0.69, 95%CI 0.53-0.88; p-interaction 0.55). The proportion of patients who discontinued study drug due to adverse events or experienced serious adverse events was similar across kidney disease etiologies, with no clear evidence of difference (p-interaction 0.04 and 0.14).

Conclusion

In patients with CKD, dapagliflozin reduced the risks of kidney failure, death from CV causes or heart failure hospitalizations, and all-cause mortality, regardless of underlying etiology of kidney disease in this study.

Funding

• Commercial Support – AstraZeneca