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October 1, 2026Arteriosclerosis Thrombosis and Vascular Biology
Empagliflozin Improves Angina and Endothelial Dysfunction Indices in Angina and No Obstructive Coronary Arteries (ANOCA)
Key result
Empagliflozin substantially lowers inflammatory and oxidative stress biomarkers vs baseline in ANOCA with CMVD.
- P<0.001
- n=11
Why the study?
Treatments targeting endothelial dysfunction in patients with angina and no obstructive coronary arteries (ANOCA) and coronary microvascular and vasomotor dysfunction (CMVD) are lacking.
Does empagliflozin improve angina and endothelial dysfunction indices in patients with ANOCA and CMVD?
Structured PICO
Does empagliflozin improve angina and endothelial dysfunction indices in patients with ANOCA and CMVD?
P
Population
11 ANOCA participants with CMVD diagnosed by invasive coronary function testing, treated with empagliflozin for 90 days.
I
Intervention
Empagliflozin 10 mg daily for 90 days
C
Comparator
Baseline (pre-treatment) and posttreatment discontinuation; also compared to stored serum from 6 ANOCA patients without CMVD
O
Outcome
Angina (Seattle Angina Questionnaire), circulating inflammatory and oxidative stress biomarkers, and endothelial microvesicles (eEVs) at 45 and 90 dayssurrogate
Main Result
p-value: p=<0.001
Empagliflozin may improve angina and reverse indices of endothelial dysfunction in patients with ANOCA and CMVD, supporting the need for larger clinical trials.
Limitations
- small sample size
- open-label design
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
LSLeandro SlipczukCardiologist, Montefiore Medical Center
“I think it's promising, but it's just not something that would change practice because of how small the trial is and the [uncontrolled, open-label] design.”
“One of the most exciting parts about the study that I honestly didn't even expect to find was a significant improvement in angina: so not only statistically significant, but clinically significant. The idea that this could be a potential new antianginal for these patients is really exciting. Of course, we need to do a clinical trial to prove that.”
VKVijay KunadianCardiologist, Newcastle University, England
“There is a need to evaluate new therapies [for ANOCA]. [With] a lot of my patients, I have been able to make them asymptomatic by increasing, say, calcium channel blockers to a very high level. But there are those few patients who still, despite doing all of [that], are symptomatic.”
Implication
May indicate endothelial benefits in ANOCA/CMVD; hypothesis-generating and requires randomized confirmation before practice change.
Abstract
BACKGROUND: Treatments targeting endothelial dysfunction in patients with angina and no obstructive coronary arteries (ANOCA) and coronary microvascular and vasomotor dysfunction (CMVD) are lacking. We evaluated the effects of SGLT2i (sodium-glucose cotransporter-2 inhibition) on angina, inflammatory and oxidative stress biomarkers, and endothelial dysfunction indices using a serum-induced in vitro model in ANOCA patients with CMVD. We conducted an open-label pilot trial of 11 ANOCA participants with CMVD diagnosed by invasive coronary function testing receiving empagliflozin (10 mg daily) for 90 days. METHODS: Angina (Seattle Angina Questionnaire), circulating inflammatory and oxidative stress biomarkers, and endothelial microvesicles (eEVs) were assessed from baseline to 45 and 90 days, and from 90 days to posttreatment discontinuation in a subset (N=5). A serum-induced in vitro model of human coronary artery endothelial cells was used to evaluate endothelial cell apoptosis, viability, eEV release, VCAM-1 (vascular cell adhesion molecule-1) expression, and mitochondrial reactive oxygen species. Stored serum from ANOCA patients without CMVD (controls, N=6) was compared with baseline samples. RESULTS: <0.001). Compared with baseline, empagliflozin significantly reduced inflammatory cytokines, oxidative stress biomarkers, and inflammatory eEVs while increasing anti-inflammatory cytokines, antioxidants, and repair eEVs at 45 and 90 days; these effects rebounded after treatment discontinuation. Similarly, serum collected during empagliflozin treatment significantly reduced endothelial cell apoptosis, eEV release, VCAM-1 expression, and mitochondrial reactive oxygen species in vitro, with reversal of these effects at posttreatment discontinuation. CONCLUSIONS: In ANOCA participants with invasive coronary function testing confirmed CMVD, SGLT2i therapy produced clinically meaningful anti-anginal effects and reversed multiple indices of endothelial dysfunction, with rebound after treatment discontinuation. These findings support further evaluation in larger clinical trials.
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Cite This Study
Tapp et al. (2026) studied Angina and No Obstructive Coronary Arteries (ANOCA) with coronary microvascular and vasomotor dysfunction (CMVD) (n=11). Empagliflozin vs. Baseline was evaluated on Angina, circulating inflammatory and oxidative stress biomarkers, and endothelial microvesicles (p=<0.001). Empagliflozin significantly reduced inflammatory cytokines, oxidative stress biomarkers, and inflammatory eEVs compared with baseline in ANOCA patients with CMVD (P<0.001).