A Systematic Review of Clopidogrel Resistance in Vascular Surgery: Current Perspectives and Future Directions

Introduction: Clopidogrel resistance is a well-described phenomenon that has been linked to adverse cardiovascular events in patients with coronary artery disease. The impact of clopidogrel resistance in patient outcomes after vascular and endovascular surgery is not well-established.

Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature review with the Medical Subject Headings (MeSH) terms "(clopidogrel resistance) and (vascular)", "(clopidogrel resistance) and (vascular surgery)", "(clopidogrel resistance) and (endovascular)", and "(clopidogrel resistance) and (endovascular surgery)" was performed in PubMed and Cochrane databases, to identify all peer-reviewed studies performed on clopidogrel resistance in vascular and endovascular surgery. Studies written in the English language from inception to 2022 were included. Case reports, studies with limited information, non-human studies, and studies not pertaining to vascular or endovascular surgery were excluded from analysis. Each study was independently reviewed by two qualified researchers to assess eligibility.

Results: Of the 691 studies identified through the MeSH strategy, 16 studies met inclusion criteria and were reviewed and summarized. These studies focused on extracranial cerebrovascular disease (n=5) and peripheral arterial disease (PAD, n=11), encompassing a total of 1,716 patients. The prevalence of clopidogrel resistance ranged from 0% to 83.3%, depending on the diagnostic assay and cutoff values used. In cerebrovascular disease, clopidogrel resistance may be associated with cerebral embolization, ischemic neurologic events, and vascular-related mortality. In PAD, clopidogrel resistance has been linked to recurrent stent thrombosis, target lesion revascularization, amputation-free survival, and all-cause mortality.

Conclusions: This systematic review provides an up-to-date summary of clopidogrel resistance in vascular and endovascular surgery. The impact of clopidogrel resistance remains incompletely investigated, and future studies are needed to clarify the role of resistance testing in patients with vascular disease.