"Dapagliflozin in Patients with Chronic Kidney Disease". The New England Journal of Medicine. 2020.
Clinical Question
In patients with chronic kidney disease, with or without type 2 diabetes, does dapagliflozin improve renal outcomes and reduce cardiovascular mortality?
Bottom Line
In patients with chronic kidney disease, dapagliflozin significantly reduced the risk of worsening kidney function, end-stage kidney disease, or death from renal or cardiovascular causes, regardless of diabetes status.
Major Points
Guidelines
Design
Multicenter, double-blind, randomized, placebo-controlled trial
N=4,304 patients with chronic kidney disease
Intervention: Dapagliflozin (10 mg once daily) (n=2,152)
Comparison: Placebo (n=2,152)
Median follow-up: 2.4 years
Primary outcome: Composite of ≥50% sustained eGFR decline, end-stage kidney disease, or death from renal or cardiovascular causes
Population
Adults with or without type 2 diabetes, eGFR of 25 to 75 ml/min/1.73m2, and urine albumin-to-creatinine ratio of 200 to 5,000
Exclusion Criteria: Type 1 diabetes, polycystic kidney disease, certain glomerulonephritides, recent immunotherapy for primary or secondary kidney disease
Interventions
Participants were randomized to receive dapagliflozin (10 mg once daily) or placebo.
Outcomes
Primary Outcome: The primary composite outcome occurred in 9.2% of the dapagliflozin group and 14.5% of the placebo group (hazard ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001; number needed to treat, 19).
Secondary Outcomes: Reduction in risk was observed for a composite of heart failure hospitalizations or cardiovascular death (hazard ratio, 0.71; P=0.009), and all-cause mortality was significantly lower in the dapagliflozin group (hazard ratio, 0.69; P=0.004).
Criticisms
The trial was stopped early due to efficacy, potentially reducing the statistical power for some secondary outcomes. Also, reversibility of the initial decline in eGFR after stopping dapagliflozin was not assessed post-trial.
Funding
Trial was funded by AstraZeneca.
Further Reading
Detailed trial information and data sharing statement available at NEJM.org.