In recent years, the introduction of sodium-glucose transporter-2 inhibitors (SGLT2is) marked a significant advancement in the treatment of cardiovascular disease (CVD). Beyond their known effects on glycemic control and lipid profile, SGLT2is demonstrate notable benefits for cardiovascular morbidity and mortality, regardless of diabetic status. These agents are currently recommended as first-line therapies in patients with heart failure, both with reduced and preserved ejection fraction, as they improve symptoms and reduce the risk of hospitalization. While several studies have demonstrated that SGLT2is can reduce the incidence of major adverse cardiovascular events (MACEs), the true impact of these agents on atherosclerosis progression and myocardial ischemia remains to be fully understood. A global beneficial effect related to improved glycemic and lipid control could be hypothesized, even though substantial evidence shows a direct impact on molecular pathways that enhance endothelial function, exhibit anti-inflammatory properties, and provide myocardial protection. In this context, this narrative review summarizes the current knowledge regarding these novel anti-diabetic drugs in preventing and treating myocardial ischemia, aiming to define an additional area of application beyond glycemic control and heart failure.

Long-term patency in complex chronic total occlusion percutaneous intervention (CTO-PCI) is often hindered by a high-risk of stent-failure (HR-SF), impacting prognosis. Drug-coated balloon (DCB) angioplasty may offer an alternative after successful crossing. We evaluated an invest-to-treat DCB strategy, determined by plaque modification results. Patients with CTO wire-crossing and suboptimal lesion profile for stenting were enrolled at Campus Bio-Medico University Hospital of Rome (April-July 2024). After plaque preparation, results were classified as good, suboptimal, or poor based on residual stenosis and thrombolysis in myocardial infarction (TIMI) flow. Poor results received conventional stenting [drug-eluting stent (DES)]. Good results underwent a nine-month follow-up; suboptimal results underwent a three-month angiography. A "redo-DCB" approach was used for persistent suboptimal results within the invest-to-treat strategy. Of 32 CTO-PCIs performed, 29 completed the nine-month follow-up. 11 patients (38%) had poor outflow and required DES (DES-group). The other 18 patients (62%) were managed with DCB alone: six patients (21%) achieved good immediate results (DCB-group), and 12 (41%) were treated as "DCB-investment" due to suboptimal plaque modification (DCB-investment group). At the three-month follow-up, four patients (14%) showed improved angiographic results, while six (21%) had suboptimal outcomes and received redo-DCB after plaque modification; two (7%) of these required DES. At nine-months, 14 patients (48%) were successfully treated with a DCB-only approach. This prospective study demonstrates that a DCB strategy for CTO patients with HR-SF is feasible and safe. A DCB-only approach resulted in favorable early outcomes for most patients. In the case of suboptimal initial results, the redo-DCB strategy emerged as a promising alternative to extensive stenting.