A review of clopidogrel resistance in lower extremity arterial disease

Lower extremity arterial disease (LEAD) is a prevalent condition that produces a significant burden on health care systems. Patients with LEAD have an increased risk of major adverse cardiovascular events as well as major adverse limb events. Despite significant variation in guidance on antiplatelet therapy for LEAD worldwide, many governing bodies recommend clopidogrel as the preferred single anti-platelet agent. Clopidogrel is also used frequently in post-revascularization regimens, either as a single agent or as part of dual antiplatelet therapy. Clopidogrel is a thienopyridine prodrug that is metabolized in the liver by the CYP2C19 enzyme. Genetic variations in CYP2C19 are common and can influence an individual's ability to metabolize clopidogrel to its active metabolite.

This work completes a narrative review of the literature to consider whether CYP2C19 genetic testing should be routinely implemented in patients who are to be prescribed clopidogrel to improve outcomes in patients with LEAD.

Recent advances in both cardiac and stroke medicine have demonstrated a role for patient genotyping to identify poor clopidogrel metabolizers and adopt alternative therapeutic strategies in these patient groups. This approach has been shown to improve clinical outcomes and has been incorporated into national and international guidance. Research studies suggest an association between CYP2C19 loss of function alleles and adverse outcomes in patients with LEAD taking clopidogrel.

The introduction of a precision medicine strategy in vascular surgery may have the potential to significantly improve clinical outcomes in this complex group of patients with multiple comorbidities.