Long-term empagliflozin therapy reduces cardiorenal disease progression in patients with chronic kidney disease
Presenter: William G. Herrington, MD, University of Oxford, Oxford, Oxfordshire, United Kingdom
A 2-year follow-up study showed that empagliflozin continues to improve cardiorenal outcomes in patients with chronic kidney disease, even if it is discontinued.
Long-term treatment with empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is necessary in patients with chronic kidney disease (CKD) to maximize cardiorenal clinical benefits, according to a 2-year post-trial follow-up study of the EMPA-KIDNEY trial presented at Kidney Week 2024.
The EMPA-KIDNEY trial first assessed the cardiorenal effects of 2 years of treatment with the SGLT2 inhibitor empagliflozin versus placebo in a broad range of patients (N=6,609) with CKD who were at risk for disease progression, noted abstract author William G. Herrington, MD, University of Oxford, Oxfordshire, United Kingdom. Participants were randomized based on their estimated glomerular filtration rates (eGFR) into two groups: 20 to less than 45 mL/min/1.73 m² or 45 to less than 90 mL/min/1.73 m² plus urine albumin-to-creatinine ratio (ACR) of 200 mg/g or more. Participants received empagliflozin for a median of 2 years.
For this post-trial follow-up of EMPA-KIDNEY, investigators observed tested how benefits evolve once the study drug stops during an additional 2 years of off-study treatment in 4,895 patients. While no study drug was issued during the post-trial period, practitioners could prescribe any SGLT2 inhibitor. Results showed that the average SGLT2 inhibitor use post-trial was 43% in the empagliflozin group and 40% in the placebo group. That lack of between group difference, Dr. Herrington said, enabled an assessment for any carry-over effects from the EMPA-KIDNEY treatment period.
Results for the post-trial follow-up study showed that empagliflozin treatment reduced the primary outcome of cardiovascular death or kidney disease progression in 26.2% of the empaliflozin group versus 30.3% in the placebo group (HR 0.79; 95% CI 0.72-0.87). Overall, there was a 13% risk reduction (HR 0.87; 95% CI 0.76-0.99).
During the first post-trial year, a primary outcome occurred in 5.7% and 7.1% of empagliflozin and placebo group participants, respectively (HR 0.76; 95% CI 0.60-0.96). In the second post-trial year, the respective rates were 12.7% and 13.6% (HR 0.9; 95% CI 0.75-1.07). Overall event rates for all post-trial periods were 19.8% and 21.4% for the empagliflozin and placebo groups, respectively, and for active plus post-trial periods, rates were 26.2% and 30.3%, respectively (HR 0.79; 95% CI 0.72-0.87). In key subgroups (diabetes, eGFR and urine ACR), relative effects on the primary outcome were similar.
The analysis showed important residual cardiorenal benefits in the empagliflozin group after the study drug was discontinued, Dr. Herrington noted. The carry-over effect of a 13% relative reduction in risk for the primary outcome in follow-up, however, was less than the 28% risk observed during the active trial.
Dr. Herrington concluded that “Any post-trial benefits appeared to last for only about 12 months, so maximizing cardiorenal benefits of SGLT2 inhibitors in chronic kidney disease requires long-term treatment.”
Funding
- Commercial Support – Boehringer Ingelheim