Empagliflozin reduces risk of disease progression and death in high-risk CKD patients: NEJM

The findings were presented at Kidney Week 2022 and published in the NEJM (New England Journal of Medicine).

Empagliflozin received its first approval from FDA in 2014 for type 2 diabetes. Since then, it is also used for risk reduction of hospitalization for heart failure and cardiovascular death irrespective of ejection fraction.

There is no proper understanding of the effects of empagliflozin in chronic kidney disease patients at risk for disease progression. Therefore, the EMPA-KIDNEY trial was designed to investigate the effects of empagliflozin treatment in a broad range of such patients.

For this purpose, the researchers enrolled CKD patients with an eGFR (estimated glomerular filtration rate) of at least 20 but less than 45 ml per minute per 1.73 m2 of a body-surface area or those having an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio of at least 200.

Patients were randomly assigned to receive 10 mg once daily of empagliflozin or a matching placebo. The study's primary outcome was a composite of kidney disease progression or death from cardiovascular causes. Progression of kidney disease was defined as end-stage kidney disease, a sustained decrease in eGFR of ≥40% from baseline, a sustained reduction in eGFR to <10 ml per minute per 1.73 m2, or death from renal causes. A total of 6609 patients underwent randomization.

The study led to the following findings:

• Kidney disease progression or death from cardiovascular causes occurred in 13.1% of patients in the empagliflozin group and 16.9% in the placebo group (hazard ratio, 0.72) During a median of 2.0 years of follow-up.
• Results were consistent in diabetes patients or those without diabetes and across subgroups defined per eGFR ranges.
• In the empagliflozin group, the hospitalization rate from any cause was lower versus the placebo group (hazard ratio, 0.86). Still, the researchers found no significant between-group differences concerning the composite outcome of heart failure hospitalization or cardiovascular-related deaths (which occurred in 4.0% of empagliflozin group patients and the placebo group 4.6%) or death from any reason (in 4.5% and 5.1%, respectively).
• The rates of serious adverse events were comparable in the two groups.

"Empagliflozin therapy led to a reduced risk of kidney disease progression or death from cardiovascular causes than placebo in a wide range of patients with CKD who were at risk for disease progression," the researchers concluded.

Reference:

EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Mayne KJ, Ng SYA, Sammons E, Zhu D, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney D, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Petrini M, Massey D, Eilbracht J, Brueckmann M, Landray MJ, Baigent C, Haynes R. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2022 Nov 4. doi: 10.1056/NEJMoa2204233. Epub ahead of print. PMID: 36331190.