Abstract
Peripheral artery disease (PAD) is a major cause of morbidity and mortality but it is usually underdiagnosed and undertreated. Patients with PAD present dysregulated procoagulant, anticoagulant, and fibrinolytic pathways leading to arterial and venous thrombosis. The risk of several ischemic-related complications could be mitigated with appropriate antithrombotic therapy, which plays a central role in all types of PAD. For years, antiplatelets have been indicated in patients with symptomatic PAD or those who have undergone revascularization. Unfortunately, a non-negligible proportion of patients with PAD will suffer from adverse events during the follow-up, even despite proper medical therapies for the prevention of PAD complications. Thus, there is room for improving clinical outcomes in these patients. Given the implication of both, primary and secondary hemostasis in arterial thrombosis and the pathophysiology of PAD, the combination of antiplatelets and anticoagulants has emerged as a potential antithrombotic alternative to antiplatelets alone. In this narrative review article, we have highlighted the most recent evidence about antithrombotic therapy in PAD patients, with a special focus on oral anticoagulation. Certainly, COMPASS and VOYAGER PAD trials have shown promising results. Thus, rivaroxaban in combination with aspirin seem to reduce cardiovascular outcomes with a similar bleeding risk compared to aspirin alone. Nevertheless, results from real-world studies are needed to confirm these observations, and other trials will provide novel evidence about the safety and efficacy of emerging anticoagulant agents.
Highlights
Peripheral artery disease (PAD) is a major cause of morbidity and mortality
It is well known that coagulation activation and endothelial stimulation are significantly increased in patients with PAD, and these factors are intimately related with the severity of the arterial disease [1]
We focus on antithrombotic therapy in lower extremity artery disease (LEAD), as this is the most common condition
Summary
Peripheral artery disease (PAD) is a major cause of morbidity and mortality. It is well known that coagulation activation and endothelial stimulation are significantly increased in patients with PAD, and these factors are intimately related with the severity of the arterial disease [1]. Elevated platelet activation, altered fibrinogen levels, thrombin generation, and fibrin turnover are typical in PAD [2] These patients, especially those with critical limb threatening ischemia, present decreases in natural anticoagulants (proteins C and S) and coagulation factors FIX, FXI, and FXII [3]. In the Framingham Study, 75% of PAD patients died from cardiovascular events, observing that in patients with intermittent claudication, mortality was 2–3 times higher [23]. With these key clinical outcomes in mind, evidence-based management of PAD includes cholesterol reduction, blood pressure and glucose level control, physical exercise therapy, and smoking cessation. We focus on antithrombotic therapy in LEAD, as this is the most common condition
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