The impact of antithrombotic therapy on endothelial function and clinical outcomes in peripheral arterial disease

Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis and is associated with substantial cardiovascular morbidity and mortality. Endothelial dysfunction represents an early and critical event in the pathogenesis of atherosclerosis and is strongly linked to adverse cardiovascular and limb events. Antithrombotic therapy is a cornerstone of secondary prevention in PAD, however, its effects on endothelial function and their relationship with clinical outcomes remain incompletely understood. This thesis investigates the impact of antithrombotic therapy on endothelial function and clinical outcomes in PAD. First, carotid artery reactivity testing, a simple, non-invasive method to evaluate endothelial function, is explored with a focus on the feasibility of handheld ultrasound devices. Second, the effects of dual-pathway inhibition with low-dose rivaroxaban and aspirin on endothelial function, vascular inflammation, and coagulation activity are evaluated in patients with PAD. Third, current and emerging evidence on antithrombotic treatment strategies in PAD is reviewed, including comparative effectiveness, safety, and the potential role of CYP2C19 genotype-guided therapy. In addition, the thesis includes studies on endothelial dysfunction, vascular inflammation, and coagulation activity following COVID-19 infection, reflecting the broader relevance of endothelial health in cardiovascular disease. Together, the findings of this thesis contribute to a better understanding of endothelial dysfunction in PAD and support more personalized and evidence-based approaches to secondary cardiovascular prevention.