medwireNews: The primary findings of the DAPA-CKD trial show that dapagliflozin significantly slows decline in kidney function in patients with chronic kidney disease (CKD) irrespective of whether they have type 2 diabetes.
The trial enrolled patients with an estimated glomerular filtration rate (eGFR) of 25 to 75 mL/min per 1.73 m2 and a urinary albumin-to-creatinine ratio of 200 to 5000 mg/g (22.6–565 mg/mmol) who were already receiving standard treatment for CKD.
Reporting at the European Society of Cardiology 2020 digital congress, Hiddo Heerspink (University of Groningen, the Netherlands) said that the investigators had recruited on the basis of needing 681 primary endpoint events to demonstrate a 22% protective effect for dapagliflozin versus placebo. However, the trial was stopped after 408 events due to “overwhelming efficacy.”
The primary endpoint was a composite of a sustained 50% or greater reduction in eGFR, end-stage renal disease, and renal or cardiovascular death. Over a median follow-up of 2.4 years there were 197 such events among the 2152 people randomly assigned to receive dapagliflozin 10 mg/day compared with 312 among the 2152 taking placebo, giving a highly significant 39% relative risk reduction.
In all, 68% and 67% of participants in the dapagliflozin and placebo groups, respectively, had type 2 diabetes. Heerspink reported that the magnitude of dapagliflozin’s protective effect was significant regardless of whether the study participants had diabetes or not, at relative risk reductions of 36% and 50%, respectively.
Regarding the individual primary endpoint components in the overall study population, there were significant reductions with dapagliflozin versus placebo for eGFR decline and end-stage renal disease, whereas the number of renal deaths was too small to calculate significance, and there was a numerical, but not statistically significant, reduction in cardiovascular mortality risk.
There was also a large risk reduction for the “clinically meaningful and patient-oriented endpoint” of chronic dialysis, kidney transplantation, and renal death, said the presenter, with dapagliflozin reducing this risk by a significant 34% (71 events vs 103 with placebo).
Last year the DAPA-HF trial showed that dapagliflozin reduced the risk for cardiovascular death and heart failure hospitalization in people with heart failure. “We now demonstrate similar effects, but in people with chronic kidney disease,” said Heerspink, reporting a significant 29% risk reduction in DAPA-CKD.
All-cause mortality risk was also reduced, by 31%, although independent commentator Diederick Grobbee (University Medical Center Utrecht, the Netherlands) noted that the source of this survival advantage remains unclear, given the lack of significance for cardiovascular mortality, despite this accounting for two-thirds of deaths in the trial. He suggested that inaccurate classification might be an issue.
Grobbee observed that the benefits of dapagliflozin were seen despite patients already receiving guideline treatment for CKD, but said: “You may wonder if this is indeed the way to go – add drug on drug on drug. At some point you might wish to replace one for another that’s more beneficial.”
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