Drug-coated balloons (DCBs) have emerged as an increasingly valuable option for the treatment of coronary artery disease (CAD). Percutaneous coronary intervention (PCI) with DCBs enables the localized delivery of antiproliferative drugs directly to the target coronary lesion, avoiding the need for permanent scaffold implantation. Historically, paclitaxel-coated balloons (PCBs) have been the most used device in this context. Paclitaxel interferes with intracellular microtubule function, leading to cell cycle arrest. However, its cytotoxicity at a higher dosage and narrow therapeutic range has raised some safety concerns. To address these issues, sirolimus-coated balloons (SCBs) have been introduced as an alternative. Sirolimus acts as a cytostatic agent with potent anti-inflammatory and antiproliferative properties and is characterized by a wider therapeutic range, potentially offering a safer profile. Several experimental and clinical studies comparing the safety and efficacy of PCBs versus SCBs have yielded mixed results. Recently, a novel DCB (SirPlux Duo), which simultaneously releases both paclitaxel and sirolimus, has been tested in a porcine coronary model with promising results. In this review, we will elucidate the mechanisms of action of paclitaxel and sirolimus, examine contemporary preclinical and clinical evidence comparing PCB and SCB angioplasty, and discuss novel devices that may enhance the safety and efficacy of PCI with DCBs.

Background: the pathophysiological mechanisms underlying spontaneous coronary artery dissection (SCAD) remain incompletely understood. Inflammation may play a pivotal role by promoting vascular susceptibility to SCAD. This study aimed to evaluate pericoronary adipose tissue (PCAT) attenuation, a recognized imaging marker of vascular inflammation, in patients with SCAD. Methods: patients with SCAD who underwent coronary computed tomography angiography (CCTA) within 48 h of the index event and with an identifiable trigger were included. Patients were classified according to the trigger preceding the event (emotional vs. physical). PCAT attenuation was measured in culprit and non-culprit vessels in all patients. Results: A total of 25 SCAD patients were included (mean age 55 ± 11 years, 80.0% female). Emotional triggers were reported in 17 patients (68.0%), while 8 (32.0%) experienced a physical trigger. Type 2 dissections were more common in the emotional trigger group (64.7% vs. 25.0%, p = 0.040). Patients with emotional triggers exhibited higher PCAT attenuation compared with those with physical triggers in the SCAD-related vessel (−62.35 ± 6.46 HU vs. −70.86 ± 8.45 HU; p = 0.028) and in non-culprit vessels (−61.39 ± 7.24 HU vs. −71.16 ± 5.28 HU; p = 0.001). Conclusions: patients with SCAD demonstrated elevated PCAT attenuation, particularly in those with emotional triggers, in both culprit and non-culprit vessels. These findings suggest that vascular inflammation may represent a predisposing factor for SCAD and a target for preventive and therapeutic strategies.

Ischemia with non-obstructive coronary arteries (INOCA) is a chronic coronary condition associated with poor prognosis and reduced quality of life. The increasing use of invasive assessments of microcirculatory function and provocative spasm testing has significantly advanced the understanding of INOCA’s pathophysiology, which ranges from coronary microvascular dysfunction to vasomotor disorders. However, the optimal management and therapeutic approach for INOCA remain to be determined. Significant sex-based differences in the pathophysiology of INOCA have been reported, resulting in variations in prevalence, phenotype, and natural history between male and female patients. The aim of this narrative review is to provide a comprehensive overview of the sex-specific pathophysiological mechanisms underlying INOCA and to summarize the differences in INOCA phenotype and prognosis. Additionally, we will explore the current knowledge on management and therapy, with the goal of advancing towards sex-based personalized treatment strategies for INOCA.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated significant benefits in cardiovascular outcomes trials, but their effect on atherosclerotic plaques remains unclear. This review aims to summarize the current evidence on the impact of SGLT2i on atherogenesis. Methods: A systematic search was conducted across PubMed, Embase, Scopus, Web of Science, and Google Scholar databases up to August 2025. Preclinical and clinical studies on the effect of SGLT2i on atherogenesis and atherosclerotic plaque extent and phenotype were included. Results: A total of 27 studies were included. Twenty-four studies examined in vitro and animal models of atherosclerosis exposed to SGLT2i, while three studies focused on the effects of SGLT2i on coronary plaques in patients with ischemic heart disease. SGLT2is modulate atherogenesis through multiple mechanisms: prevention and reversal of endothelial dysfunction, reduction in monocyte recruitment and promotion of anti-inflammatory macrophage polarization. Additionally, SGLT2is reduce inflammation and inhibit vascular calcification. Through these mechanisms, SGLT2is decrease plaque burden in both diabetic and non-diabetic atherosclerosis models. Furthermore, they reduce lipid content and macrophages accumulation while increasing fibrous cap thickness, thereby contributing to plaque stabilization. Conclusions: Preclinical and clinical evidence suggest that SGLT2is modulate every step of the atherogenic process, reduce atherosclerotic burden and promote coronary plaque stabilization.

Background/Objectives: Diabetes mellitus (DM), especially insulin-dependent DM (IDDM), is strongly associated with adverse outcomes following percutaneous coronary intervention (PCI) failure. Polymer-free drug-eluting stents (PF-DESs) have emerged as a promising strategy to mitigate long-term coronary inflammation. This study aimed to evaluate the role of PF-DES, as compared to permanent-polymer DES (PP-DES) and biodegradable-polymer DES (BP-DES), in a real-world cohort of IDDM patients with obstructive coronary artery disease (CAD) undergoing PCI. Methods: IDDM patients with CAD who underwent PCI with DES at Parma University Hospital were divided into two study groups: PF-DES group vs. BP/PP-DES group. The primary endpoint was target vessel failure (TVF) at the 4-year follow-up. Survival analyses and propensity score matching (PSM) were performed to account for baseline differences. Results: A total of 170 IDDM patients with 215 treated lesions (31.6% PF-DES; 68.4% BP/PP-DES) were included. The PF-DES group experienced significantly lower rates of TVF (10.3% vs. 27.2%, p < 0.01, log rank p = 0.0072) compared with the BP/PP-DES group. PSM analysis confirmed the good clinical performance of PF-DES (HR 0.27, p < 0.01). Conclusions: In this PSM-based observational study, PF-DESs were associated with significantly lower rates of TVF compared with BP/PP-DESs in IDDM patients undergoing PCI for CAD. These suggest that PF-DES may represent a personalized PCI strategy for IDDM patients, with prognostic benefits that become increasingly pronounced as the clinical and anatomical risk profile worsens.

Antithrombotic therapy plays a pivotal role in reducing thromboembolic complications, including stroke and valve thrombosis, following Transcatheter Aortic Valve Implantation (TAVI). However, the benefits of such therapy must be balanced against the increased risk of major bleeding events. The optimal antithrombotic strategy in this setting remains a matter of ongoing debate, given the heterogeneity of patient profiles and procedural variables. Among TAVI recipients, women represent a growing proportion and exhibit distinct anatomical, physiological, and clinical characteristics that influence both thrombotic and bleeding risk. Compared to men, women more frequently experience vascular complications and major bleeding events, despite better survival outcomes. These differences are driven by smaller vessel caliber, higher vascular tortuosity, and altered platelet reactivity. Consequently, sex-specific risk stratification is essential when considering antiplatelet or anticoagulant regimens post-TAVI. This review provides a comprehensive synthesis of current evidence regarding antithrombotic strategies in the post-TAVI setting, with a dedicated focus on sex-related differences. Particular emphasis is placed on the female population, assessing ischemic and hemorrhagic outcomes and the implications for long-term management. Improving outcomes in women undergoing TAVI necessitates tailored antithrombotic strategies that balance efficacy and safety. Ongoing research and dedicated trials are essential to refine these strategies and to inform future guideline updates in this expanding patient population.