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 (T2DM), independently of the presence of concomitant cardiovascular disease.
Prof. John McMurry (University of Glasgow, Scotland) presented a new analysis of the randomised, double-blind, placebo-controlled DAPA-CKD trial, 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 62 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=0.000000028). The primary outcome was reduced by 36% (HR 0.64) in patients with T2DM and by 50% in patients without diabetes (HR 0.50). In addition, dapagliflozin was associated with a significant reduction in all 3 secondary endpoints compared with placebo, namely:
- a 31% reduction in risk of all-cause mortality (HR 0.69; P=0.0035);
- a 29% reduction in hospitalisation for heart failure or cardiovascular death (HR 0.71; P=0.0089); and
- a 44% reduction in worsening function or death from kidney failure (HR 0.56; P<0.0001).
The new analysis presented at the AHA Scientific Sessions, and simultaneously published in the journal 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 diabetes. However, mean eGFR and median urinary albumin-to-creatinine ratio were similar between the 2 groups.
Cardiovascular outcomes were worse in the group with cardiovascular disease, but kidney failure occurred at the same rate in both groups. Dapagliflozin treatment reduced the risk of the primary composite outcome to a similar extent in both patients without cardiovascular disease (HR 0.61; 95% CI 0.48-0.78) and those with cardiovascular disease (HR 0.61; 95% CI 0.47-0.79; P-interaction=0.90). Likewise, the composite outcome of heart failure hospitalisation or cardiovascular death was also similar across groups (HR 0.67; 95% CI 0.40-1.13 vs HR 0.70; 95% CI 0.52-0.94, respectively; P-interaction=0.88), and all-cause (HR 0.63; 95% CI 0.41-0.98 vs HR 0.70; 95% CI 0.51-0.95, respectively; P-interaction=0.71). Adverse events were low overall and did not differ between patients with or without cardiovascular disease. These data conclusively demonstrate that dapagliflozin benefits CKD patients regardless of the presence or absence of cardiovascular disease.
- McMurray J, et al. Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease. Session FS.02, Virtual AHA Scientific Sessions 2020, 13-17 Nov.
- Heerspink HJL, et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446.
- McMurray J, et al. Effect of Dapagliflozin on Clinical Outcomes in Patients with Chronic Kidney Disease, With and Without Cardiovascular Disease. Circulation 2020; Nov 13. Doi:1161/CIRCULATIONAHA.120.051675.
