Small vessel coronary artery disease represents a frequent challenge in percutaneous coronary intervention, particularly affecting women and patients with diabetes mellitus or chronic kidney disease. While definitions vary across clinical trials using reference vessel diameter thresholds between 2.5 and 3.0 millimeters, a standardized cutoff below 2.5 millimeters measured via intracoronary imaging has been proposed, as angiography often underestimates true vessel diameter. These lesions carry elevated risks of restenosis and target lesion failure compared to larger vessels. New-generation drug-eluting stents with thinner struts remain the primary treatment option. However, drug-coated balloon strategies offer a compelling alternative for de novo small vessel disease, with paclitaxel-coated balloons demonstrating clinical outcomes comparable to second-generation drug-eluting stents over three years while eliminating permanent metallic scaffolds and reducing dual antiplatelet therapy duration. This distinction matters because the benefit does not extend to vessels 3.0 millimeters or larger, and performance varies across devices, with sirolimus-coated balloon effectiveness dependent on coating formulation. These advances enable more personalized treatment strategies for this prevalent subset of coronary lesions.

The ARCADIA-ZERO registry evaluated two-year clinical outcomes comparing complex and non-complex percutaneous coronary intervention (PCI) procedures utilizing the Resolute Onyx zotarolimus-eluting stent. This prospective multicenter study assessed safety and efficacy of this advanced stent technology across diverse patient populations and lesion complexities. The registry tracked major adverse cardiovascular events, stent thrombosis, restenosis rates, and target lesion revascularization in both patient cohorts over the 24-month follow-up period. The Resolute Onyx platform, designed with enhanced biocompatibility features, demonstrated consistent performance in managing intricate coronary anatomy and high-risk presentations. Findings from ARCADIA-ZERO provide critical real-world evidence regarding stent performance beyond controlled trial settings, informing clinical decision-making for interventional cardiologists. Understanding differential outcomes between complex and non-complex cases helps optimize patient selection and procedural strategies, ultimately improving long-term cardiovascular outcomes and reducing repeat interventions. This registry contributes valuable data to the interventional cardiology community regarding contemporary stent technologies and their application across varying disease complexity levels.

This single-center retrospective study examined 301 chronic coronary syndrome patients who underwent elective percutaneous coronary intervention with physiological assessments using the PressureWire Aeris guidewire at Tsuchiura Kyodo General Hospital between January 2011 and June 2024. Researchers stratified patients into tertiles based on delta QFR-FFR, the difference between quantitative flow ratio and fractional flow reserve measurements obtained before and after intervention. The study excluded patients with prior percutaneous coronary intervention, myocardial infarction history, multivessel disease, or coronary artery bypass grafting due to potential confounding effects on microvascular function and major adverse cardiovascular events. The lowest tertile comprised 101 patients with delta QFR-FFR values below −0.057. This research investigates the clinical significance of discrepancies between these two non-invasive and invasive physiological assessment techniques in guiding coronary intervention decisions, contributing to understanding of optimal lesion evaluation strategies in chronic coronary syndrome management.

For patients with an acute coronary syndrome event, current guidelines recommend dual antiplatelet therapy for at least 12 months after drug-eluting stent placement. However, several clinical trials have assessed whether continuing dual antiplatelet therapy beyond 12 months is beneficial. We review the pros and cons of extending dual antiplatelet therapy.

Coronary Artery Disease remains a critical global health challenge, necessitating accurate severity assessment to guide clinical treatment decisions. The SYNTAX score, derived from X-ray coronary angiography images, is fundamental to this evaluation but suffers from manual scoring limitations including time consumption and inter-observer variability. Researchers from Vellore Institute of Technology have developed VMamba-QAG-Net, a novel five-stage computational pipeline that automates SYNTAX score estimation directly from angiography images. The system employs advanced image processing techniques including Bilateral Filtering and CLAHE preprocessing, visual mamba scanning with Quantum Attention Gates for vessel segmentation, and anatomical labeling of 27 distinct coronary artery segments using a Vessel Prototype Memory Bank. Subsequent stages extract vessel centerlines, calculate percentage diameter stenosis using perpendicular ray casting, and detect stenotic lesions via the Aquila Optimizer before computing the final SYNTAX score. Evaluation on the ARCADE dataset demonstrated strong performance, with a Dice coefficient of 0.9070 and accuracy of 0.9841 for binary segmentation, and a Dice coefficient of 0.7512 for multi-class segmentation. These results indicate VMamba-QAG-Net's potential to substantially support cardiologists in clinical decision-making and treatment planning.

Researchers from Wuhan University conducted a retrospective, propensity-score-matched case-control study to evaluate how metabolic indices predict in-stent restenosis (ISR) following percutaneous coronary intervention. The study analyzed 774 patients—387 with ISR and 387 matched controls—comparing three metabolic markers: the triglyceride-glucose (TyG) index, atherogenic index of plasma (AIP), and metabolic score for insulin resistance (METS-IR). Using multivariable modeling and receiver operating characteristic curve analysis, researchers found that the baseline clinical-procedural model achieved an AUC of 0.716 for ISR prediction. Adding TyG improved discrimination to AUC 0.756, while AIP demonstrated superior performance at AUC 0.772, both showing statistically significant improvements. METS-IR provided no incremental benefit. Bootstrap analyses confirmed that TyG and AIP, but not METS-IR, enhanced predictive discrimination. For ISR severity assessment, both TyG and AIP yielded only modest, non-significant improvements. These findings suggest that AIP and TyG are valuable metabolic biomarkers for stratifying restenosis risk in coronary intervention patients, potentially enabling more personalized risk assessment and clinical management strategies.

This retrospective comparative cohort study examined clinical outcomes in hemodynamically stable ST-segment elevation myocardial infarction (STEMI) patients with multivessel coronary artery disease. The research compared two percutaneous coronary intervention (PCI) strategies: multivessel PCI, where all stenotic vessels are treated during the acute phase, versus culprit-only PCI, which targets only the infarct-related artery. The study evaluated twelve-month clinical outcomes including major adverse cardiac events, mortality rates, reinfarction, and target lesion revascularization in both cohorts. This comparison addresses a significant clinical controversy regarding optimal revascularization strategy in complex STEMI cases. The findings contribute to evidence-based guidance for interventional cardiologists treating hemodynamically stable patients with multivessel disease, informing decisions about complete versus staged revascularization approaches during acute myocardial infarction management.

This open-access research article, published in the American Journal of Cardiovascular Drugs in September 2026, examines temporal trends and predictors of P2Y12 inhibitor selection and switching among acute coronary syndrome (ACS) patients following percutaneous coronary intervention (PCI). P2Y12 inhibitors—antiplatelet medications including clopidogrel, prasugrel, and ticagrelor—are critical components of dual antiplatelet therapy post-PCI. The study investigates how clinician selection of these agents has evolved over time and identifies factors influencing medication switching patterns. By analyzing these trends, the research provides insight into real-world prescribing practices and potential drivers of treatment changes in ACS management. Understanding P2Y12 inhibitor utilization patterns is clinically significant as these medications directly impact thrombotic and bleeding outcomes in coronary intervention patients. The findings contribute valuable evidence regarding optimal antiplatelet strategy implementation and may inform future clinical decision-making in acute coronary syndrome care.

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Siemens Healthineers has developed vFFR (vessel Fractional Flow Reserve), a software solution that derives coronary physiology assessments directly from angiographic image data to evaluate hemodynamic significance of coronary lesions. This non-invasive technique eliminates the need for invasive pressure-wire based hyperemic FFR measurements, which currently serve as the gold standard. The technology has undergone rigorous clinical validation through the FAST study series, culminating in the FAST III trial—a multicenter European study of 2,235 patients across 37 sites conducted in partnership with the European Cardiovascular Research Institute and Pie Medical Imaging under Dr. Joost Daemen's leadership. The trial compared vFFR-guided percutaneous coronary intervention against traditional FFR guidance in patients with stable coronary artery disease or non-ST elevation acute coronary syndrome requiring physiological assessment of intermediate lesions. Recently presented results at the American College of Cardiology conference confirmed vFFR's non-inferiority to wire-based FFR while offering significant advantages: reduced invasiveness, faster assessment, and lower procedural costs. vFFR is now integrated into Siemens' ARTIS icono and pheno platforms as QuantWeb vFFR and available as a standalone CAAS vFFR application, with table-side operation capabilities via ARTIS Touch UI.

The AIR-STEMI trial, presented at ESC Congress 2026 and published in the NEJM, investigates optimal strategies for treating multivessel disease following ST-segment myocardial infarction. While complete revascularization within 45 days is guideline-recommended, determining which non-culprit lesions require intervention remains challenging. Traditional wire-based physiology proves cumbersome in acute settings, whereas functional coronary angiography offers a wire-free alternative, deriving fractional flow reserve estimates and physiological pullback data directly from angiographic images without pharmacological hyperaemia. This investigator-initiated, multicenter randomized trial enrolled 1,823 patients across 21 centers in Italy and Pakistan. Patients with successful culprit-lesion PCI and at least one non-culprit lesion with 50-99% diameter stenosis were randomly assigned to complete revascularization guided by either functional coronary angiography or conventional angiography. The trial evaluates physiology as an integrated strategy incorporating physiological pullback to guide PCI planning, rather than a simple binary tool. This approach promises to reduce overtreatment while optimizing outcomes in acute coronary syndromes with multivessel involvement.

Researchers from Fuwai Yunnan Hospital conducted a prospective randomized controlled trial comparing two interventional strategies for treating small coronary vessel disease. The study evaluated the non-inferiority of paclitaxel-coated balloons against rapamycin-eluting metal stents in patients with de novo non-complex lesions. Paclitaxel-coated balloons represent an emerging alternative to traditional drug-eluting stents, utilizing drug-delivery technology through balloon coating rather than permanent metal implants. The trial addresses growing clinical interest in drug-coated balloon angioplasty as a potentially effective treatment option for small-vessel coronary disease, where stent placement carries specific challenges. Published in Advances in Interventional Cardiology, this research contributes to the expanding body of evidence supporting drug-coated balloons as viable alternatives to conventional stent therapy, potentially offering patients reduced long-term complications from metallic implants while maintaining therapeutic efficacy in treating coronary artery narrowing.

The Journal of Clinical Medicine's special issue on advances in antithrombotic therapy addresses the evolving landscape of cardiovascular treatment. Antithrombotic agents—antiplatelet and anticoagulant medications—have significantly reduced ischemic events across acute coronary syndromes, atrial fibrillation, and peripheral artery disease. However, clinicians face the ongoing challenge of balancing ischemic protection against bleeding risk. The field is shifting from standardized treatment approaches toward personalized medicine, employing escalation and de-escalation strategies for antiplatelet therapy intensity tailored to individual patient profiles. Novel agents under clinical investigation, including factor XI inhibitors and subcutaneous P2Y12 receptor inhibitors, show promise in optimizing the ischemia-bleeding trade-off. The special issue, edited by Dr. Daniele Giacoppo and Dr. Antonio Greco, encompasses key topics including antiplatelet therapy in coronary artery disease, antithrombotic strategies in high-risk complex percutaneous coronary intervention, emerging pharmacological agents targeting thrombosis and coagulation, bleeding complication management, perioperative antithrombotic strategies, and guideline implementation. This comprehensive collection reflects the field's commitment to advancing patient outcomes through evidence-based, precision medicine approaches.

Across studies, pooled AUCs were 0.84 for RF, 0.74 for LR, 0.73 for DNN/MLP, and 0.59 for SVM; RF heterogeneity was extreme. Exploratory RF subgroup analysis showed an AUC of 0.91 in DES-only cohorts versus 0.72 in mixed BMS/DES cohorts. Age and lipid-related variables were most frequently reported, followed by sex and diabetes, supporting external validation.

Ticagrelor monotherapy after abbreviated DAPT lowers bleeding without increasing ischemic events, providing a favorable net clinical benefit in high-risk PCI patients and supporting guideline trends toward shorter DAPT.

Coronary artery disease remains the leading cause of global morbidity and mortality, traditionally managed through percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). However, this review examines the critical importance of concurrent optimal medical therapy (OMT) alongside revascularization procedures. OMT encompasses antiplatelet agents, lipid-lowering drugs for all patients, beta-blockers and ACE inhibitors or angiotensin receptor blockers for most patients, complemented by cardiac risk factor management and lifestyle modifications. For stable angina patients, OMT represents the recommended initial treatment, with revascularization indicated only when symptoms persist despite optimal medical management or when prognosis improvement is expected. Following acute coronary syndromes or revascularization procedures, long-term OMT significantly improves clinical outcomes and patient prognosis. While revascularization techniques have revolutionized CAD treatment, the concomitant use of evidence-based OMT remains vital for maximizing therapeutic benefits and ensuring optimal patient outcomes in contemporary practice.

Recent studies of platelet endothelial cell adhesion molecule-1 (PECAM-1 [CD31])-deficient mice have revealed that this molecule plays an important role in controlling the activation and survival of cells on which it is expressed. In this review, we focus on the complex cytoplasmic domain of PECAM-1 and describe what is presently known about its structure, posttranslational modifications, and binding partners. In addition, we summarize findings that implicate PECAM-1 as an inhibitor of cellular activation via protein tyrosine kinase–dependent signaling pathways, an activator of integrins, and a suppressor of cell death via pathways that depend on damage to the mitochondria. The challenge of future research will be to bridge our understanding of the functional and biochemical properties of PECAM-1 by establishing mechanistic links between signals transduced by the PECAM-1 cytoplasmic domain and discrete cellular responses.

The role of platelets in hemostasis and thrombosis is dependent on a complex balance of activatory and inhibitory signaling pathways. Inhibitory signals released from the healthy vasculature suppress platelet activation in the absence of platelet receptor agonists. Activatory signals present at a site of injury initiate platelet activation and thrombus formation; subsequently, endogenous negative signaling regulators dampen activatory signals to control thrombus growth. Understanding the complex interplay between activatory and inhibitory signaling networks is an emerging challenge in the study of platelet biology, and necessitates a systematic approach to utilize experimental data effectively. In this review, we will explore the key points of platelet regulation and signaling that maintain platelets in a resting state, mediate activation to elicit thrombus formation, or provide negative feedback. Platelet signaling will be described in terms of key signaling molecules that are common to the pathways activated by platelet agonists and can be described as regulatory nodes for both positive and negative regulators.

While current oral antiplatelet therapies benefit many patients, they deregulate the hemostatic balance leaving patients at risk of systemic side-effects such as hemorrhage. Dual antiplatelet treatment is the standard approach, combining aspirin with P2Y12 blockers. These therapies mainly target autocrine activation mechanisms (TxA2, ADP) and, more recently, the use of thrombin or thrombin receptor antagonists have been added to the available approaches. Recent efforts to develop new classes of anti-platelet drugs have begun to focus on primary platelet activation pathways such as through the immunoreceptor tyrosine-based activation motif (ITAM)-containing collagen receptor GPVI/FcRγ-chain complex. There are already encouraging results from targeting GPVI, with reduced aggregation and smaller arterial thrombi, without major bleeding complications, likely due to overlapping activation signaling pathways with other receptors such as the GPIb–V–IX complex. An alternative approach to reduce platelet activation could be to inhibit this signaling pathway by targeting the inhibitory pathways intrinsic to platelets. Stimulation of endogenous negative modulators could provide more specific inhibition of platelet function, but is this feasible? In this review, we explore the potential of the two major platelet immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing inhibitory receptors, G6b-B and PECAM-1, as antithrombotic targets.

Platelets are not only crucial for hemostasis but also play a vital role in a wide range of physiological and pathological processes. The continuous expansion of knowledge in platelet biology holds significant therapeutic implications, offering new avenues for treating various diseases. Sustained research and innovation in platelet-targeted therapies, coupled with a deeper understanding of their molecular mechanisms, will pave the way for novel and more effective treatment approaches, ultimately improving patient outcomes and advancing medical science.