Dapagliflozin reduces renal risk independent of CV disease status

A new analysis from the DAPA-CKD trial found that the SGLT2 inhibitor dapagliflozin reduced the risk of kidney failure, death from cardiovascular causes or hospitalisation for heart failure, and prolonged survival in people with chronic kidney disease (CKD), with or without type 2 diabetes mellitus (T2DM). The benefits of dapagliflozin were independent of the presence of cardiovascular disease (CVD) [1,2].

Prof. John McMurray (University of Glasgow, Scotland) presented a new analysis of the randomised, double-blind, placebo-controlled DAPA-CKD trial (NCT03036150), which enrolled 4,304 patients to assess the impact of dapagliflozin 10 mg versus placebo alongside standard of care (i.e. ACE inhibitor or ARB) [1]. Participants had a urinary albumin to creatinine ratio of ≥200 mg/g and an estimated glomerular filtration rate (eGFR) between 25–75 mL/min/1.73 m². The average age was 61.8 years, 66.9% were male, and 67.5% had T2DM. The primary endpoint was a composite of sustained decline in eGFR of ≥50%, end-stage renal disease, and renal or cardiovascular-related mortality.

The overall results of the trial were recently published in the New England Journal of Medicine [2]. Briefly, after a median follow-up of 2.4 years, 197 primary events occurred with dapagliflozin compared with 312 events with placebo (HR 0.61; 95% CI 0.51–0.72; P<0.0001). The primary outcome was reduced by 36% (HR 0.64; 95% CI 0.52–0.79) in patients with T2DM and by 50% in patients without T2DM (HR 0.50; 95% CI 0.35–0.72). In addition, dapagliflozin was associated with a significant reduction in all 3 secondary endpoints compared with placebo, namely:

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    • a 31% reduction in risk of all-cause mortality (HR 0.69; 95% CI 0.53–0.88; P=0.0035);
    • a 29% reduction in hospitalisation for HF or CV death (HR 0.71; 95% CI 0.55–0.92; P=0.0089); and
    • a 44% reduction in worsening kidney function or death from kidney failure (HR 0.56; 95% CI 0.45–0.68; P<0.0001).

The new analysis presented at the AHA Scientific Sessions and simultaneously published in Circulation [3] looked at primary and secondary outcomes based on baseline CV disease status. Patients from the DAPA-CKD cohort with cardiovascular disease at baseline (n=1,610; 37.4%) were older, more often male, had a higher blood pressure and body-mass index, and were more likely to have T2DM. However, mean eGFR and median urinary albumin-to-creatinine ratio were similar between the 2 groups.

Patients with known CVD had higher event rates, but kidney failure occurred at the same rate in both groups. Among patients with and without CVD at baseline, positive results for dapagliflozin were maintained versus placebo (see Table). Adverse events were low overall and did not differ between patients with or without CVD. These data conclusively demonstrate that dapagliflozin benefits CKD patients regardless of the presence or absence of cardiovascular disease.

Table: Primary and secondary outcomes by baseline CV disease [1]
CI, confidence interval; CV, cardiovascular disease; eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease.

 

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   1. McMurray J, et al. Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease. FS.02, AHA Scientific Sessions 2020, 13–17 Nov.
   2. Heerspink HJL, et al. N Engl J Med. 2020 Oct 8;383(15):1436–1446.
   3. McMurray J, et al. Circulation 2020; Nov 13. Doi:1161/CIRCULATIONAHA.120.051675.

 



Posted on 18 February 202117 May 2024