The coronary no-reflow phenomenon remains a daunting and unresolved barrier during percutaneous coronary procedures, especially for acute coronary syndrome. Despite successful epicardial artery patency restoration, decreased microvascular perfusion leads to unfavorable outcomes such as ventricular remodeling, progression of heart failure, and increased mortality. This review provides a new, integrative informative perspective by combining multifactorial pathophysiology, which includes systemic inflammation, thrombogenicity, ischemia–reperfusion injury, and distal embolization, with advances in diagnostic imaging, such as cardiac magnetic resonance and computed tomography. Therapeutic options, including antithrombotic regimes, vasodilators, and mechanical adjuncts, are evaluated in the context of developing debates and unmet clinical needs. Importantly, we provide feasible future directions for artificial intelligence-based predictive modeling and targeted microvascular treatments. This comprehensive review fills a significant gap, aiming to inform personalized approaches and improve both short- and long-term outcomes in this high-risk patient population.

Drug-coated balloon (DCB) therapy differs fundamentally from stent-based revascularization since the vessel itself becomes the treatment substrate. Consequently, vascular preparation is an important component of DCB therapy. This review therefore examines contemporary vessel preparation before DCB therapy across coronary and peripheral interventions, integrating lesion morphology, procedural outcomes, intravascular imaging, and clinical follow-up. Across vascular beds, the objective is not maximal plaque disruption, but sufficient modification of the dominant mechanical limitation to achieve predictable expansion, controlled vessel injury, and effective balloon–vessel wall contact. Subsequent failure after coronary DCB therapy has been associated with residual plaque burden and calcium morphology. Specialty balloons, atherectomy and intravascular lithotripsy have been associated with improved procedural success, lumen expansion, and calcium modification, with lower rates of flow-limiting dissection or bailout stenting in selected settings. Randomized evidence has generally demonstrated more consistent procedural than long-term clinical benefits. Moreover, much of the evidence supporting advanced calcium-modification strategies derives from stent-based interventions and cannot be directly extrapolated to DCB-only therapy. These findings favor a lesion-specific, preparation-dependent approach rather than routine escalation to increasingly aggressive technologies. Conventional balloons may be sufficient for mechanically responsive lesions, whereas scoring or cutting balloons, atherectomy, or intravascular lithotripsy should be selected according to lesion morphology and the specific mechanical limitation that persists after initial preparation. Intravascular imaging may facilitate objective assessment of a “DCB-ready” vessel, although validated preparation thresholds remain undefined. The question is thus not which preparation device is preferable but whether the vessel has been adequately prepared to receive the drug. Future studies should go beyond device-to-device comparisons and assess whether predefined, imaging-based preparation targets improve drug delivery, vessel healing, and durable clinical outcomes. The next step toward precision DCB therapy across coronary and peripheral disease may be to shift the focus from device selection to treatment-substrate optimization.

Background: Current ESC guidelines recommend the use of oral anticoagulant therapy in patients with atrial fibrillation to reduce the risk of arterial embolization. Recently, Factor XIa inhibitors were investigated as an alternative to the commonly used DOACs. Aims: This systematic review and meta-analysis aim to assess whether Factor XIa inhibitors lead to lower risks of bleeding compared to DOACs in patients with atrial fibrillation. Methods: PubMed, Cochrane, and EMBASE were searched. The primary endpoint was the occurrence of a composite of Major or clinically relevant non-major bleeding. Secondary endpoints included death from any cause, cardiovascular death, any adverse effects, any serious adverse effects, minor bleeding, stroke, or systemic embolism. Results: A total of 3 studies met the inclusion criteria and were included in the qualitative and quantitative analysis, comprising 16,772 patients. Factor XIa inhibitors were associated with significantly fewer major or clinically relevant non-major bleedings than DOACs (RR = 0.40 [95% CI [0.32, 0.51]), I² = 3%, p < 0.00001). There were no differences between Factor XIa inhibitors and DOACs regarding the occurrence of death (RR = 0.83 [95% CI 0.63, 1.08]), I² = 0%, (p = 0.15) and cardiovascular death (RR = 1.09 [95% CI 0.74, 1.63]), I² = 0%, (p = 0.65). Interestingly, the risk of stroke and systemic embolism was higher among the patients exposed to factor XIa inhibitors compared to the DOACs group RR = 6.05 [95% CI [1.02, 35.94]), I² = 5%, (p = 0.05). Conclusions: Factor XIa inhibitors are superior to DOACs in terms of bleeding complications. However, this meta-analysis shows a significantly higher risk of stroke or systemic embolism as compared to commonly used DOACs.