Study: Empagliflozin Reduces MACE Regardless of Baseline Albuminuria Levels

According to a poster presentation at the American College of Cardiology 2024 annual meeting, treatment with empagliflozin (Jardiance; Boehringer Ingelheim) was associated with a reduced incidence of major adverse cardiovascular events (MACE) in patients with cardiovascular disease regardless of baseline albuminuria levels, highlighting its potential use across the spectrum of kidney function.¹

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Enpagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor with a large body of data showing its effectiveness in reducing the risk of cardiovascular events among patients with heart failure with or without diabetes. More recent data have shown that empagliflozin slowed the progressive decline in kidney function in this patient population.¹ Notably, data from the EMPA-KIDNEY phase 3 trial (NCT03594110) supported its recent FDA approval to reduce the risk of sustained decline in estimated glomerular filtration rate (eGFR), end-stage kidney disease, cardiovascular death, and hospitalization for adults with chronic kidney disease (CKD) at risk of progression.²

The EMPA-KIDNEY trial included more than 6600 patients and found that empagliflozin plus standard of care demonstrated a 28% relative risk reduction, with an absolute risk reduction of 3.6% per patient-year at risk, compared with placebo in the primary endpoint of kidney disease progression or cardiovascular death. Kidney disease progression was defined as end-stage kidney disease, a sustained decline in eGFR to below 10 mL/min/1.73 m2, kidney death, or sustained decline of at least 40% in eGFR from randomization.²

Furthermore, the event rate in the empagliflozin group was 13.1% compared with 16.9% in the placebo arm.² This approval, granted in September 2023, is the fourth FDA approval for empagliflozin based on data from the EMPOWER program.²

In the poster presented at ACC, investigators pooled data from the EMPEROR-Pooled, EMPA-KIDNEY, and EMPA-REG OUTCOME clinical trials. The incidence of MACE was categorized as the primary endpoint according to albumin-to-creatinine ratio (UACR) and dichotomous data were pooled as overall response (OR) and 95% confidence interval (CI) and analyzed in a random effect model.¹

A total of 23,347 patients were included in the analysis, with a mean age of 66.7 years and a mean follow-up of 3 years. Of those, 11,051 had normoalbuminuria (UACR <30 mg/g), 6973 had microalbuminuria (UACR 30-300 mg/g), and 5211 had macroalbuminuria (UACR >300 mg/g).¹

According to the results, empagliflozin was associated with a lower risk of MACE across all 3 UACR categories (OR=0.85, 95% CI: 0.76 to 0.97 for normoalbuminuria; OR=0.8, 95% CI: 0.7-0.91 for microalbuminuria; OR=0.76, 95% CI: 0.67-0.87 for macroalbuminuria).² In addition to the previous data from the EMPA-KIDNEY trial, this new analysis further highlights the benefit of empagliflozin across the spectrum of kidney function.

References

1. Abdelaziz A, Hafez A, Elaraby A, Atta K, Diab RA, Abdellatif M, et al. Empagliflozin and Cardiovascular Outcomes Across the Spectrum of Kidney Functions: A Pooled Analysis of 23347 Patients. Poster. Presented at: American College of Cardiology 2024. April 7, 2024. https://www.abstractsonline.com/pp8/#!/10973/presentation/11595

2. Gallagher A. FDA Approves Empagliflozin for Adults With Chronic Kidney Disease at Risk of Progression. Pharmacy Times. September 22, 2023. Accessed April 5, 2024. https://www.pharmacytimes.com/view/fda-approves-empagliflozin-for-adults-with-chronic-kidney-disease-at-risk-of-progression