Peri-treatment of SGLT-2 Inhibitor on Myocardial Infarct Size and Remodeling Index in Patients With Acute Myocardial Infarction and High Risk of Heart Failure Undergoing Percutaneous Coronary Intervention

Overview

We aimed to identify whether SGLT-2 inhibitor administration before and after coronary intervention is effective in reducing the size of infarction and myocardial remodeling in patients with acute myocardial infarction (AMI) and high risk of heart failure, and its mechanism. For this reason, we compared cardiac magnetic resonance imaging (CMR) parameters and clinical outcomes between the SGLT-2 inhibitor group and the control group to confirm the efficacy and safety of SGLT-2 inhibitors.

After the introduction of percutaneous coronary intervention (PCI) as a method to normalize blood flow in the treatment of coronary artery disease, not only the technical aspects of coronary intervention but also the devices and medications have been improved over the past 30 years. However, despite these advances, morbidity, and mortality of AMI are still high. In particular, in patients with ST-segment elevation MI (STEMI), the 1-year mortality rate and hospitalization rate due to heart failure are 10%, and 22%, respectively. Accordingly, various efforts are being made to improve the prognosis of AMI and to reduce the infarct size, which is a major prognostic factor. The most effective method for achieving this goal to early and successful revascularization by PCI. However, restoring blood flow, which is a prerequisite for relieving ischemia, can paradoxically cause damage to the myocardium and death of the myocardium by itself. This phenomenon is called myocardial reperfusion injury. Several pharmacological and mechanical treatments targeting this phenomenon have been studied, and the experimental and small-scale clinical trials have been shown to have the effect of reducing infarct size and relieving myocardium.4 However, to date, large-scale clinical trials have not demonstrated clinical benefits. SGLT-2 inhibitors are developed to lower blood sugar and treat type 2 diabetes mellitus (DM) by inhibiting Sodium glucose co-transporter-2 in proximal renal tubule, releasing glucose into the urine and preventing reabsorption. However, SGLT-2 inhibitors are known to have an effect on lowering cardiovascular events in addition to lowering blood sugar. In three large-scale, multicenter, randomized trials to evaluate the effects of SGLT-2 in type 2 diabetic patients, the combined outcome consisting of cardiac death or readmission due to heart failure was significantly lowered compared to the placebo group. In particular, DECLARE-TIMI 58 trial confirmed that this effect was consistent regardless of the history of atherosclerotic cardiovascular disease or heart failure.8 In addition, DAPA-CKD trial showed that SGLT-2 inhibitor significantly reduced the composite outcome consisting of cardiovascular death or readmission due to heart failure as well as the kidney-related outcome compared to the placebo group in patients with chronic kidney disease regardless of type 2 DM. Similarly, EMPEROR-Reduced and DAPA-HF trials consistently demonstrated that SGLT-2 inhibitor was associated with significantly lower risk of a composite of cardiovascular death or worsening heart failure in patients with heart failure with reduced ejection fraction. Therefore, the current guideline recommended the use of SGLT-2 inhibitor in patients with heart failure with reduced ejection fraction, with a conjunction of goal-directed medical therapy. Nevertheless, the mechanism that can explain this has been extensively investigated, but it is not clear yet. Several potential hypotheses have been proposed as mechanisms such as increased natriuresis, decreased blood pressure, decreased inflammation, and decreased reactive oxidative stress. In this regard, it is anticipated that the use of SGLT-2 inhibitors will benefit even in patients with AMI and high risk of heart failure in both acute and chronic phases. Therefore, we aimed to identify whether SGLT-2 inhibitor administration before and after coronary intervention is effective in reducing the size of infarction and myocardial remodeling in patients with AMI and high risk of heart failure, and its mechanism. For this reason, we compared CMR parameters and clinical outcomes between the SGLT-2 inhibitor group and the control group to confirm the efficacy and safety of SGLT-2 inhibitors.