medwireNews: Empagliflozin continues to have cardiorenal benefits for patients with chronic kidney disease (CKD) up to 12 months after discontinuation, indicates research reported in The New England Journal of Medicine.
The findings follow publication of the EMPA-KIDNEY trial, in which empagliflozin 10 mg/day was shown to have positive cardiorenal effects compared with placebo in patients with CKD who were at increased risk for disease progression.
The follow-up trial focused on 4891 consenting patients who had survived the initial 2-year study period. The participants had a baseline estimated glomerular filtration rate (eGFR) of between 20 and less than 45 mL/min per 1.73 m2 or a rate of between 45 and less than 90 mL/min per 1.73 m2 plus a urinary albumin-to-creatinine ratio of at least 200.
During the follow-up 2-year monitoring phase, no trial empagliflozin or placebo was given, but local practitioners could prescribe open-label sodium-glucose cotransporter (SGLT)2 inhibitors, including empagliflozin. This occurred in a similar proportion of participants in the original empagliflozin (43%) and placebo groups (40%).
Throughout the trial and post-trial follow-up, the primary composite outcome of kidney disease progression – defined as a sustained reduction in eGFR of 40% or higher, end-stage kidney disease, a sustained eGFR level below 10 mL/min per 1.73 m2, or death from kidney failure – occurred in 26.2% of 3304 of the empagliflozin group and in 30.3% of 3305 of the placebo group, with a hazard ratio (HR) of 0.79 in favor of empagliflozin. The HR for a primary outcome event in the post-trial period only was a significant 0.87 with empagliflozin versus placebo.
“Much of the post-trial benefit regarding the primary-outcome event occurred early,” the researchers say, with significant HRs of 0.60 and 0.76 for the first 6 and 12 months, respectively, before reaching a nonsignificant 0.90 after 24 months.
William Herrington (University of Oxford, UK) and co-investigators say that kidney progression over the full 4-year study period occurred in significantly fewer empagliflozin-treated patients than controls (23.5 vs 27.1%, HR=0.79), as did any-cause death or end-stage kidney disease (16.9 vs 19.6%, HR=0.81). Cardiovascular death was also significantly lower with empagliflozin than placebo treatment (3.8 vs 4.9%, HR=0.75) but the rate of non-cardiovascular death was 5.3% in both groups.
The authors reason that if there had not been an ongoing empagliflozin treatment effect after discontinuation, the HR in the post-trial period would have been 1.0 and “absolute benefits would be observed to diminish.”
Herrington et al reflect: “In relative terms, the carry-over effect on the primary-outcome event was less than the effect of receiving empagliflozin during the active-trial period and appeared to last for up to 12 months, with most additional benefit seen in the first 6 months after the active trial ended.”
They conclude: “This finding suggests that the maximization of cardiorenal clinical benefits of SGLT2 inhibitors in chronic kidney disease requires long-term treatment.”
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