A review of clopidogrel resistance in lower extremity arterial disease

IntroductionLower extremity arterial disease (LEAD) is a prevalent condition which produces a significant burden on healthcare 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 which is metabolised in the liver by the CYP2C19 enzyme. Genetic variations in CYP2C19 are common and can influence an individual’s ability to metabolise clopidogrel to its active metabolite.MethodsThis 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.ResultsRecent advances in both cardiac and stroke medicine have demonstrated a role for patient genotyping in order to identify poor clopidogrel metabolisers 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.ConclusionsThe 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 co-morbidities.