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Heerspink HJL, Stefansson BV, Correa-Rotter R, et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24. (Original study)
Abstract

BACKGROUND: Patients with chronic kidney disease have a high risk of adverse kidney and cardiovascular outcomes. The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known.

METHODS: We randomly assigned 4304 participants with an estimated glomerular filtration rate (GFR) of 25 to 75 ml per minute per 1.73 m2 of body-surface area and a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 200 to 5000 to receive dapagliflozin (10 mg once daily) or placebo. The primary outcome was a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes.

RESULTS: The independent data monitoring committee recommended stopping the trial because of efficacy. Over a median of 2.4 years, a primary outcome event occurred in 197 of 2152 participants (9.2%) in the dapagliflozin group and 312 of 2152 participants (14.5%) in the placebo group (hazard ratio, 0.61; 95% confidence interval [CI], 0.51 to 0.72; P<0.001; number needed to treat to prevent one primary outcome event, 19 [95% CI, 15 to 27]). The hazard ratio for the composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal causes was 0.56 (95% CI, 0.45 to 0.68; P<0.001), and the hazard ratio for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI, 0.55 to 0.92; P = 0.009). Death occurred in 101 participants (4.7%) in the dapagliflozin group and 146 participants (6.8%) in the placebo group (hazard ratio, 0.69; 95% CI, 0.53 to 0.88; P = 0.004). The effects of dapagliflozin were similar in participants with type 2 diabetes and in those without type 2 diabetes. The known safety profile of dapagliflozin was confirmed.

CONCLUSIONS: Among patients with chronic kidney disease, regardless of the presence or absence of diabetes, the risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo. (Funded by AstraZeneca; DAPA-CKD ClinicalTrials.gov number, NCT03036150.).

Ratings
Discipline Area Score
Nephrology 7 / 7
Internal Medicine 7 / 7
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Comments from MORE raters

Internal Medicine rater

More and more studies on these newer diabetic agents and multiple positive effects - this in patients even without DM! This for CKD!

Internal Medicine rater

Interesting trial showing a benefit even in the absence of diabetes. Calculated NNT is 19 with an absolute risk reduction of 5.3%. Should be considered as therapy.

Nephrology rater

It is refreshing to know that we can use SGLT1 inhibitors for patients with Stage 3-4 CKD and it is quite beneficial in reducing bad CV outcomes and also in protecting kidney function in these patients as in non-CKD patients. Very good news for renal patients and nephrologists.

Nephrology rater

Adults with or without diabetes with eGFR 25 to 75 and UACR 23-560 mg/mmol were randomly assigned to receive dapagliflozin 10 mg once daily. Over 2.4 years, the primary outcome (death from CV or kidney causes or dialysis for >=28 days, kidney transplantation or eGFR <15 for >=28 days) occurred in 9.2% in the dapagliflozin group and 14.5% in the placebo group, an absolute risk reduction of 5% and an NNT of 20. No differences in this effect were seen in any pre-specified subgroup. People with and without diabetes and people across the range of UACR and eGFR benefitted. There was no increase in amputation or Fournier's gangrene. We have not had a new intervention in the management of CKD since RASi. This is important information for primary care, general internists, endocrinologists and nephrologists. In general, people who meet study entry criteria are not managed by nephrologists, who tend to be referred and to manage patients with more advanced CKD.
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