The effect of SGLT2 inhibitors on silent myocardial ischemia

Abstract Background In large cardiovascular (CV) outcome trials, sodium-glucose co-transporter 2 (SGLT2) inhibitors reduced the development of heart failure (HF) in patients with type 2 diabetes (T2DM). Also it reduced CV death and worsening HF events in HFrEF patients. It is unknown whether SGLT2 inhibitors work through glucose-dependent mechanism or it could have other effects not related to glucose on cardiovascular morbidity and mortality in diabetic patients. Its effect on silent ambulatory myocardial ischemia (SAMI) has not been reported yet. In this study we report the effect of SGLT2 inhibitors on (SAMI). Treating silent myocardial ischemia has a prognostic effect and may improve long term mortality of chronic ischemic heart disease (CIHD). Methods We enrolled 44 type 2 diabetic patients with proven stable coronary artery disease (CAD) and at least one episode of on silent ambulatory myocardial ischemia (SAMI) on ambulatory ECG monitoring. All of them were receiving optimal therapy for CIHD and type 2 DM. 22 patients were randomized to receive Dapagliflozin 5mg qd and the other 22 patients received placebo. Ambulatory monitoring was repeated after 4 to 6 months of therapy. The two groups were comparable with respect to baseline characteristics, number of episodes of ST-segment depression, HgbA1c level, and baseline serum cholesterol levels. Holters were read by a blinded cardiologist. Results The Dapagliflozin group experienced a significant reduction in the number of episodes of ST-segment depression compared with the placebo group. ST-segment depression completely resolved in 8 of 22 patients (36%) in the Dapagliflozin group versus 3 of 22 (13%) in the placebo group and the Dapagliflozin group exhibited a highly significant reduction in (SAMI) (P<0.001). By logistic regression, treatment with Dapagliflozin was an independent predictor of (SAMI) resolution. Conclusions Therapy with SGLT2 inhibitors in type2 DM patients results in reduction or resolution of (SAMI) recorded as episodes of ST-segment depression in ambulatory monitoring of the ECG. A larger study is required to confirm this theory and to see the effect of SAMI reduction on long term mortality of CIHD in diabetics. Possible mechanisms for this beneficial effects of SGLT2i includes: Reduction in oxygen supply-demand mismatch, improvement in cardiac microvascular function, modulation of cardiac energy metabolism, reduction in glucotoxicity, reduction in sympathetic nervous system activation and reduction in blood pressure. Funding Acknowledgement Type of funding source: None