Genetic variants that reduce the effectiveness of clopidogrel may increase the risk of heart attack and stroke in patients undergoing peripheral artery disease (PAD) interventions, according to research presented at VAM 2026.
The study found that around one in five patients carried single nucleotide polymorphisms (SNPs) that impair the body’s ability to convert clopidogrel into its active form. While those patients did not experience higher rates of adverse limb outcomes after revascularization, they were significantly more likely to experience major adverse cardiovascular events over the following year.
“Our purpose was really to look at whether patients who are poor metabolizers of clopidogrel, which is our standard antiplatelet regimen following peripheral interventions, would have poorer outcomes,” said Edith Tzeng, MD, senior author on the study.
Investigators linked pharmacogenomic testing results with patients who underwent peripheral vascular interventions to evaluate whether carriers of the relevant SNPs experienced different outcomes than patients without the variants. The primary outcomes included both major adverse limb events, such as repeat revascularization or major amputation, and major adverse cardiovascular events, including myocardial infarction and stroke.
Although the genetic variants were not associated with increased limb complications, they were linked to a higher risk of cardiovascular events.
“Patients with PAD have a four-times increased risk of coronary artery events than patients who are just diagnosed with coronary artery disease,” said senior author Katherine Reitz, MD. “It is a relevant finding despite it not being directly related to the intervention itself.”
The findings add to growing interest in using pharmacogenomic information to personalize antiplatelet therapy. Alternative medications that do not require metabolic activation are already available, but they carry a greater bleeding risk and are not routinely prescribed for all patients.
Rather than making an immediate practice recommendation, Tzeng and Reitz said the study highlights an important unanswered question.
“These relevant genotypes that we’ve known about for at least 20 years are still relevant and we still have no answer,” said Reitz. “As genomic information becomes increasingly accessible, this is another thing we need to think about when we’re prescribing for patients.”
