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Clinical Summary

Dapagliflozin Benefits CKD Patients With and Without Cardiovascular Disease

Takeaway

  • Dapagliflozin reduced the risk of kidney failure, death from cardiovascular (CV) causes or hospitalisation for heart failure (HF) and death from any cause in patients with chronic kidney disease (CKD) with or without type 2 diabetes (T2D), irrespective of history of CV disease (CVD) at baseline.

Why this matters

  • The combined cardio-renal benefits of sodium-glucose cotransporter 2 inhibitors in patients with CKD with and without T2D are substantial, whether there is a history of CVD or not.

Study design

  • In the DAPA-CKD trial, 4304 patients with CKD with and without T2D were randomly assigned to receive dapagliflozin or placebo.
  • In this prespecified subgroup analysis, patients were divided into those with (secondary prevention group, n=1610) and without baseline CVD (primary prevention group, n=2694).
  • Primary outcome: composite of ≥50% decline in estimated glomerular filtration rate, end-stage kidney disease or kidney or CV death.
  • Secondary outcomes: kidney composite outcome (primary endpoint, minus CV death), the composite of hospitalisation for HF or CV death and all-cause death.
  • Funding: AstraZeneca.

Key results

  • Dapagliflozin lowered the risk of the primary composite outcome to a similar extent in both the primary (HR, 0.61; 95% CI, 0.48-0.78) and secondary (HR, 0.61; 95% CI, 0.47-0.79) prevention groups (Pinteraction=.90).
  • Dapagliflozin reduced the risk of the following outcomes to a similar extent in both the primary and secondary prevention groups:
    • composite of HF hospitalisation or CV death (HR, 0.67; 95% CI, 0.40-1.13 and HR, 0.70; 95% CI, 0.52-0.94, respectively; Pinteraction=.88); and
    • all-cause death (HR, 0.63; 95% CI, 0.41-0.98 and HR, 0.70; 95% CI, 0.51-0.95, respectively; Pinteraction=.71).
  • Overall, the rates of adverse events were low and similar in the primary and secondary prevention groups.

Limitations

  • Certain events were infrequent and the effect of therapy on these could not be assessed reliably.
 

McMurray JJV, Wheeler DC, Stefánsson BV, Jongs N, Postmus D, Correa-Rotter R, Chertow GM, Greene T, Held C, Hou FF, Mann JFE, Rossing P, Sjöström CD, Toto RD, Langkilde AM, Heerspink HJL. Effect of Dapagliflozin on Clinical Outcomes in Patients with Chronic Kidney Disease, With and Without Cardiovascular Disease. Circulation. 2020 Nov 13 [Epub ahead of print]. doi: 10.1161/CIRCULATIONAHA.120.051675. PMID: 33186054View abstract

This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.

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