ESC 2020 — Dapagliflozin benefits CKD patients with and without diabetes

  • Sarfaroj Khan
  • Conference Reports
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  • Sodium-glucose cotransporter-2 inhibitor dapagliflozin reduced the risk for kidney failure, death from cardiovascular (CV) causes or heart failure hospitalization, and all-cause mortality in patients with chronic kidney disease (CKD) with and without type 2 diabetes.

Why this matters

  • Findings highlight dapagliflozin’s potential to benefit patients with CKD who are in need of improved treatment options.

Study design

  • In this DAPA-CKD trial, 4304 patients (mean age, 61.8 years; 66.9% male) were randomly assigned in a ratio of 1:1 to receive dapagliflozin 10 mg or placebo once daily in addition to standard of care (i.e., an angiotensin-converting enzyme [ACE] inhibitor or an angiotensin II receptor blocker [ARB]).
  • All patients had an estimated glomerular filtration rate (eGFR) ≥25 and ≤75 mL/min/1.73m2; urinary albumin-to-creatinine ratio between ≥200 mg/g and ≤5000 mg/g; and were on a stable, maximum tolerated dose of an ACE inhibitor or ARB for ≥4 weeks (unless contraindicated).
  • Primary composite endpoint: sustained ≥50% eGFR decline, end-stage kidney disease (ESKD), and renal or CV death.
  • Funding: AstraZeneca.

Key results

  • During a median follow-up of 2.4 years, 197 primary endpoint events occurred in the dapagliflozin group vs 312 in the placebo group (HR, 0.61; 95% CI, 0.51-0.72; P=.000000028).
  • The benefit was consistent for patients with (HR, 0.64; 95% CI, 0.52-0.79) and without (HR, 0.50; 95% CI, 0.35-0.72) type 2 diabetes (Pinteraction=.24).
  • Dapagliflozin reduced all 3 secondary endpoints compared with placebo:
    • sustained ≥50% eGFR decline, ESKD, and renal death (HR, 0.56; 95% CI, 0.45-0.68; P<.0001>
    • CV death or heart failure hospitalization (HR, 0.71; 95% CI, 0.55-0.92; P=.0089); and
    • all-cause mortality (HR, 0.69; 95% CI, 0.53-0.88; P=.0035).
  • Serious adverse events were slightly more in the placebo vs dapagliflozin group (33.9% vs 29.5%) and the number that discontinued the drug was similar (5.7% vs 5.5%).

Expert commentary

Janani Rangaswami, MD, from the Einstein Medical Center in Philadelphia, PA said: "The sooner you intervene the better," to slow further progression, but the new findings show "benefit even when treating patients with lower eGFRs. There is still hope to prevent or delay dialysis."