Data from the EMPA-KIDNEY post-trial follow-up (PTFU) reveals that empagliflozin continues to provide cardiorenal benefits for approximately one year after discontinuation in patients with chronic kidney disease (CKD). The findings, presented at The American Society of Nephrology (ASN) Kidney Week 2024, highlight the sustained impact of empagliflozin on key clinical outcomes.
Will Herrington, Professor of Trials and Epidemiology of Kidney Disease at Oxford University, noted the unexpected substantial carryover effect of empagliflozin. "We weren't expecting to see such a substantial carryover effect... this carryover effect was having effects on hard clinical outcomes," he told HCPLive.
EMPA-KIDNEY Trial Details
The EMPA-KIDNEY trial randomized participants with an eGFR between 20 and 45 or 45 and 90 and urine ACR of up to 200 mg/g to either empagliflozin or placebo for a median of 2 years. The primary composite outcome was kidney disease progression or cardiovascular death, measured during the original trial and PTFU. Open-label SGLT2 inhibitors were allowed during the trial.
In the PTFU, data from 4895 of the 6609 randomized participants were followed for a median of 2 years after discontinuing the study treatment. SGLT2 inhibitor use was similar between the empagliflozin (43%) and placebo (40%) groups during the PTFU.
Key Findings
Over the entire follow-up period, kidney disease progression or cardiovascular death occurred in 865 of 3305 (26.2%) participants who received empagliflozin and 1001 of 3305 (30.3%) who received placebo (hazard ratio [HR], 0.79 [95% CI, 0.72-0.87]). These findings were consistent across subgroups of diabetes, eGFR, and urine albumin-creatinine ratio.
Post-trial, participants initially treated with empagliflozin experienced a 13% reduction (HR, 0.87 [95% CI, 0.76-0.99]) in the risk of kidney disease progression or cardiovascular death. The absolute differences in this primary outcome were 57 (standard error [SE], 14) per 1000 at the end of the main trial and remained significant at 45 (SE, 14) per 1000 at the end of the PTFU.
Specifically, the empagliflozin group had a 23.5% risk of kidney disease progression, a 16.9% composite risk of end-stage kidney disease or death, and a 3.8% risk of cardiovascular death, compared to 27.1%, 19.6%, and 4.9% risks in the placebo group, respectively.
Clinical Implications
Herrington emphasized the importance of long-term adherence to empagliflozin. "The drug works, it will continue to work for about a year after you stop taking it. But if you stop taking it for more than a year, then you lose all of the benefits... we should be ensuring our patients stay on the drug at the at the full dose long term to ensure we maximize their benefits," he stated. These findings reinforce the sustained benefits of empagliflozin in slowing kidney disease progression and reducing cardiovascular risk in patients with CKD.
