medwireNews: Dapagliflozin reduces the risk for kidney failure, heart failure (HF) hospitalization, and death in people with chronic kidney disease (CKD), irrespective of their history of HF, DAPA-CKD study data show.
John McMurray (University of Glasgow, UK) and co-investigators say their “findings highlight the crucial value of SGLT2 [sodium-glucose cotransporter 2] inhibitors in the primary and secondary prevention of HF in patients with CKD, irrespective of history of diabetes (and the value of this class of therapy in slowing progression of CKD, irrespective of history of HF).”
For the study, 4304 individuals with CKD (estimated glomerular filtration rate [eGFR] 25–75 mL/min per 1.73 m2 plus urinary albumin-to-creatinine ratio 200–5000 mg/g) were randomly assigned to receive dapagliflozin 10 mg/day or placebo. Of these, 10.8% had a history of HF and 67.5% had type 2 diabetes.
During a median follow-up of 2.4 years, the risk for the primary composite endpoint of a 50% or greater decline in eGFR, onset of end-stage kidney disease, or death from kidney or cardiovascular disease was significantly lower among people who received dapagliflozin relative to those who did not, regardless of their HF status.
Specifically, in people with HF at baseline, the incidence of this outcome was 6.5 events per 100 patient–years with dapagliflozin versus 11.0 events per 100 patient–years with placebo, corresponding to a significant 42% risk reduction in favor of dapagliflozin.
For those without HF at baseline, there was a significant 38% lower risk for the primary composite endpoint with dapagliflozin relative to placebo, at event rates of 4.4 and 7.7 per 100 person–years, respectively.
And the researchers note that “[e]vent rates for all components of the primary outcome favored dapagliflozin, irrespective of whether patients had HF or not.”
McMurray and team also looked at a “key secondary composite outcome” consisting of HF hospitalization or cardiovascular death. The risk for this outcome was a significant 29% lower with dapagliflozin versus placebo overall, which was primarily driven by a reduction in HF hospitalizations.
In people with HF at baseline, there was a nonsignificant 38% lower risk for HF hospitalization with versus without dapagliflozin (3.9 vs 6.1 events per 100 person–years), while in those with no HF, the risk was a significant 60% lower in those who received the SGLT2 inhibitor (0.4 vs 1.0 events per 100 person–years).
The authors say that this finding highlights “the benefit of dapagliflozin in HF in patients with stage 2-4 CKD, including those without type 2 diabetes.”
In addition, the annual rate of eGFR decline was 1.03 mL/min per 1.73 m2 slower with dapagliflozin than placebo in the patients with HF at baseline and 0.93 mL/min per 1.73 m2 slower in those with no HF.
McMurray et al comment: “Although these findings do not support the hypothesis that HF accelerates decline in kidney function, longer-term follow-up is required to make a robust assessment of the impact of HF on future risk of end-stage kidney disease.”
The study data are published in JACC: Heart Failure and were also presented as an eposter at the virtual ESC Congress 2021.
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