The following are key points to remember from a JACC scientific statement on antithrombotic strategies for patients with peripheral artery disease (PAD):

1. Patients with PAD experience major cardiovascular and limb events. Antithrombotic strategies including antiplatelets and anticoagulants remain a cornerstone of treatment and prevention.
2. Recent trials have shown heterogeneity in the response to antithrombotic therapies in patients presenting primarily with PAD when compared to those presenting primarily with coronary artery disease. In addition, there is observed heterogeneity regarding the effects of antiplatelets and anticoagulants with respect to different outcomes including cardiovascular and major adverse limb events.
3. This, coupled with risks of bleeding, requires a patient-centered and holistic assessment of benefit-risk when selecting antithrombotic strategies for patients with PAD. Overall, intensive antithrombotic therapy should be considered for patients with PAD and at high risk for major adverse cardiovascular events (MACE) and major adverse limb events (MALE).
4. A global multidisciplinary work group was convened to evaluate antithrombotic strategies in PAD and to summarize the current state of the art. Common clinical scenarios around antithrombotic decision making were provided. Finally, insights with regard to implementation of future investigation were described.
5. In patients with PAD at high risk for MACE and/or MALE, more intensive antithrombotic therapy should be considered if bleeding risk is not prohibitive. Data support the use of dual pathway inhibition with low-dose rivaroxaban plus low-dose aspirin to prevent ischemic events in patients with PAD both in the chronic and post lower extremity revascularization (LER) setting.
6. The duration of dual pathway inhibition should be informed by both the procedural risk as well as other approaches to long-term risk stratification, and long-term use should be supported by the MACE, mortality, and amputation benefits observed in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial in patients who are not at high bleeding risk. Other antithrombotic combinations, such as low-dose rivaroxaban plus clopidogrel, have not yet been studied after LER and may be of interest for future clinical trials.
7. For patients presenting for coronary or other non-PAD vascular procedures, periprocedural management allows temporary cessation of rivaroxaban and a second antiplatelet agent if dual antiplatelet therapy is being used. A single antiplatelet agent should be continued through the procedure if bleeding risk is tolerable.
8. The utility of antiplatelet therapy with therapeutic anticoagulation in patients with PAD and cardioembolic acute limb ischemia has not been studied and guideline recommendations for the management of patients with atrial fibrillation and atherosclerotic vascular disease should be followed.
9. Despite a growing number of evidenced-based antithrombotic strategies in PAD, undertreatment and poor clinical translation remains a major challenge. This is largely driven by two key gaps in care. First, >50% of patients with PAD remain undiagnosed, driven by a combination of patient-level unawareness of the disease, patient-level under-reporting of symptoms, clinician-level lack of physical examination detection, and clinician-level lack of diagnostic testing. Second, even when PAD is diagnosed, guideline-level medical therapy is rarely achieved.
10. Multidisciplinary approaches and shared decision-making are necessary to optimize the type, intensity, and duration of therapy. Efforts to address the broad underuse of medical therapies and, in particular, antithrombotic therapies are needed to reduce risk and disparities in outcomes.

Clinical Topics: Anticoagulation Management, Vascular Medicine, Atherosclerotic Disease (CAD/PAD)

Keywords: Anticoagulants, Antithrombotic Therapy, Peripheral Arterial Disease, Platelet Aggregation Inhibitors

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