Impact of sodium-glucose cotransporter inhibitors in acute coronary syndrome patients on endothelial function and atherosclerosis related-biomarkers: ATH-SGLT2i pilot study

Little is known about the effects of sodium-glucose co-transporter 2 inhibitors (SGLT2i) on atherosclerosis. We aimed to determine if a 90-day intake of Dapagliflozin could improve atherosclerosis biomarkers (namely endothelial function assessed by flow-mediated dilatation [FMD] and carotid intima-media thickness [CIMT]) in diabetic and non-diabetic acute coronary syndrome (ACS) patients when initiated in the early in-hospital phase. ATH-SGLT2i was a prospective, single-center, observational trial that included 113 SGLT2i naive patients who were admitted for ACS and who were prescribed Dapagliflozin at a fixed dose of 10 mg during their hospital stay for either type 2 diabetes or for heart failure. After 90 days of follow-up, subjects who had a continuous intake of Dapagliflozin formed the SGLT2i group, while patients who did not take Dapagliflozin formed the non-SGLT2i group. In each of these main study groups, we considered diabetic and non-diabetic subgroups. The primary endpoint was the difference in between baseline and 90 days in FMD (∆FMD) and in FMD rate (∆FMD%). The secondary outcome was change in CIMT (∆CIMT). We enrolled 54 patients in the SGLT2i group aged 59 ± 9 years (70.4% males) which 30 were diabetics, and 59 in the non-SGLT2i group aged 63 ± 11 years (78% males) which 34 were diabetics. After 90 days, ∆FMD and ∆ FMD% were higher in the SGLT2i group in comparison with the non-SGLT2i group (0.05 ± 0.15 vs −0.05 ± 0.11, P < .001 and 1.78 ± 3.63 vs −0.88 ± 4, P < .001). Within the SGLT2i group, the improvement of FMD% was higher in non-diabetic patients (2.85 ± 3.46 vs 0.9 ± 3.59, P = .05). Multivariate analysis showed that Dapagliflozin intake was independently associated with FMD% improvement (HR = 2.24). After 90 days, CIMT showed no significant difference between the SGLT2i and the non-SGLT2i groups. In this pilot study, a 90-day intake of Dapagliflozin at the fixed dose of 10 mg started in the acute phase of an ACS, was associated with endothelial function improvement in diabetic and non-diabetic patients.