EMPA-KIDNEY:Cardiorenal Benefits of Empagliflozin Persist Even After Discontinuation

Study at a glance:

• Journal: New England Journal of Medicine, 2024

• Population: 6609 patients with chronic kidney disease (CKD) at risk of progression

• Method: RCT of empagliflozin (10 mg daily) vs. placebo for ~2 years, followed by a 2-year post-trial observational period without study drug

• Key Finding: Empagliflozin reduced kidney disease progression and cardiovascular death, with sustained benefits even after discontinuation

Summary:
The EMPA-KIDNEY trial and its post-trial follow-up evaluated whether the cardiorenal benefits of empagliflozin extend beyond active treatment. Patients with CKD (eGFR 20–45 ml/min/1.73m² or eGFR 45–90 with albuminuria ≥200 mg/g) were randomized to empagliflozin (n=3304) or placebo (n=3305). After ~2 years of blinded treatment, 4891 patients entered a 2-year observational phase where SGLT2 inhibitor use was balanced between groups (~40%). Across the combined trial and follow-up periods, empagliflozin lowered the risk of the composite primary outcome (kidney disease progression or cardiovascular death) by 21% compared to placebo (HR 0.79; 95% CI, 0.72–0.87). During the post-trial period alone, benefits persisted (HR 0.87; 95% CI, 0.76–0.99). Risk reductions were consistent for kidney disease progression (23.5% vs. 27.1%) and cardiovascular death (3.8% vs. 4.9%), with no impact on non-cardiovascular mortality.

Takeaway:
Empagliflozin offers durable protection against kidney disease progression and cardiovascular death in high-risk CKD patients, with benefits lasting up to 12 months after treatment discontinuation.

Source:
EMPA-KIDNEY Collaborative Group. Long-Term Outcomes after Discontinuation of Empagliflozin in Chronic Kidney Disease. N Engl J Med. 2024. doi:10.1056/NEJMoa2405244. Available at: https://www.nejm.org/doi/10.1056/NEJMoa2409183