
Empagliflozin Shown to Reduce Endothelial Dysfunction in Women With INOCA
Key Takeaways
- Empagliflozin reduced proinflammatory cytokines and oxidative stress markers in INOCA patients with CMD, improving vascular health.
- Treatment led to favorable shifts in endothelial extracellular vesicles, indicating potential benefits for endothelial function.
The drug lowered inflammation, oxidative stress, and endothelial injury markers in women with INOCA and coronary microvascular dysfunction.
The sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin demonstrated significant reductions in inflammatory and oxidative stress markers in women with ischemia and no obstructive coronary arteries (INOCA) complicated by
Although up to 70% of patients with angina undergoing coronary angiography have INOCA, treatment options remain limited, particularly for those with CMD and endothelial dysfunction (EnD).1 These patients often experience impaired myocardial blood flow and ischemia despite no evidence of obstructive coronary artery disease.
Researchers at The Christ Hospital in Cincinnati, Ohio, investigated whether empagliflozin, a therapy known for its cardiovascular benefits in diabetes and heart failure, could provide similar benefit in this high-risk group. Findings were presented at the
Circulating Biomarkers
Both abstracts focused on the same cohort: 7 women with a mean age of 63 years.
Patients with INOCA and CMD
Oxidative stress measures followed a similar trend; plasma 8-isoprostane and myeloperoxidase activity were elevated at baseline but reduced after treatment, while antioxidant capacity improved. Circulating endothelial extracellular vesicles (eEVs) also shifted favorably, with reductions in inflammatory VCAM-positive eEVs and increases in repair-associated CD34-positive eEVs. At 45 days, 2 urinary tract infections, 1 vaginal yeast infection, and 1 nonsignificant decrease in glomerular filtration rate were reported.
“This pilot study indicates that SGLT2i treatment is well tolerated and has the potential to reduce inflammation, ROS, and eEVs in INOCA patients with CMD,” the researchers said.
Endothelial Cell Dysfunction
Notably, sera collected post treatment reduced both the concentration and size of eEVs, lowered VCAM-1 expression in supernatant and cell lysates, and decreased mitochondrial reactive oxygen species staining.
“Sera from INOCA patients with CMD has an increased capacity to induce EnD compared to no-CMD controls and this capacity is reduced following SGLTi treatment,” the researchers concluded. “These results suggest SGLT2is may target the underlying mechanisms of disease (EnD and CMD) in INOCA patients.”
Together, the pilot trials highlight empagliflozin’s potential to directly influence mechanisms of EnD in patients with INOCA and CMD. Although limited by small sample size and short follow-up, the results provide early evidence that SGLT2 inhibition may improve vascular health beyond its established benefits in diabetes and heart failure.
References
- Tapp DN, Tipler P, Ashokprabhu N, et al. Empagliflozin significantly reduces circulating markers of endothelial dysfunction in ischemia with non-obstructive coronary arteries (INOCA) and coronary microvascular dysfunction: a pilot trial. Presented at: ESC Congress 2025; August 30, 2025; Madrid, Spain.
https://esc365.escardio.org/presentation/305790 - QuesadaO, TappDN, Tipler P, et al. Empagliflozin significantly reduces the capacity of sera to induce endothelial dysfunction in ischemia non-obstructive coronary arteries (INOCA): EMbArk phase II pilot trial. Presented at: ESC Congress 2025; August 29, 2025; Madrid, Spain.
https://esc365.escardio.org/presentation/305756
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