• DOI:10.1161/CIRCULATIONAHA.120.051675
• Corpus ID: 226948086

Effect of Dapagliflozin on Clinical Outcomes in Patients with Chronic Kidney Disease, With and Without Cardiovascular Disease.

@article{McMurray2020EffectOD,
  title={Effect of Dapagliflozin on Clinical Outcomes in Patients with Chronic Kidney Disease, With and Without Cardiovascular Disease.},
  author={John J. V. McMurray and David C. Wheeler and Bergur V. Stef{\'a}nsson and Niels Jongs and Douwe Postmus and Ricardo Correa-Rotter and Glenn M. Chertow and Tom Greene and Claes Held and Fan Fan Hou and Johannes F E Mann and Peter Rossing and Carl David Sj{\"o}str{\"o}m and Robert D. Toto and Anna Maria Langkilde and Hiddo J Lambers Heerspink},
  journal={Circulation},
  year={2020}
}

• J. McMurray, D. Wheeler, +13 authors H. Heerspink
• Published 27 October 2020
• Medicine
• Circulation

Background: Dapagliflozin reduces the risk of end-stage renal disease in patients with chronic kidney disease. We examined the relative risk of cardiovascular and kidney events in these patients and the effect of dapagliflozin on either type of event, taking account of history of cardiovascular disease. Methods: In the DAPA-CKD trial (Dapagliflozin And Prevention of Adverse Outcomes in Chronic Kidney Disease), 4304 participants with chronic kidney disease were randomized to dapagliflozin 10 mg once daily or placebo. The primary endpoint was a composite of sustained decline in estimated GFR ≥50%, end-stage kidney disease, or kidney or cardiovascular death. The secondary endpoints were a kidney composite outcome (primary endpoint, minus cardiovascular death), the composite of hospitalization for heart failure or cardiovascular death and all-cause death. In a prespecified subgroup analysis, we divided patients into primary and secondary prevention subgroups according to history of cardiovascular disease. Results: Secondary prevention patients (n=1610; 37.4%) were older, more often male, had a higher blood pressure and body-mass index, and were more likely to have diabetes. Mean estimated glomerular filtration rate and median urinary albumin-to-creatinine ratio was similar in the primary and secondary prevention groups. The rates of adverse cardiovascular outcomes were higher in the secondary prevention group, but kidney failure occurred at the same rate in the primary and secondary prevention groups. Dapagliflozin reduced 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 (0.61, 0.47-0.79) prevention groups (P-interaction=0.90). This was also true for the composite of heart failure hospitalization or cardiovascular death (0.67, 0.40-1.13 versus 0.70, 0.52-0.94, respectively, P-interaction=0.88), and all-cause (0.63, 0.41-0.98 versus 0.70, 0.51-0.95, respectively, P-interaction=0.71). Rates of adverse events were low overall and did not differ between patients with and without cardiovascular disease. Conclusions: Dapagliflozin reduced the risk of kidney failure, death from cardiovascular causes or hospitalization for heart failure, and prolonged survival, in people with chronic kidney disease, with or without type 2 diabetes, independently of the presence of concomitant cardiovascular disease Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03036150.