High Yield of Pharmacogenetic Testing for Clopidogrel Resistance in a Canadian Outpatient Stroke Population

BACKGROUND: Clopidogrel is commonly prescribed for secondary stroke prevention, but routine pharmacogenetic testing is not typically performed. As the CYP2C19 enzyme activates clopidogrel into its effective form, clopidogrel-treated patients who carry CYP2C19 loss-of-function alleles may face an increased risk of recurrent stroke. We examined the prevalence of CYP2C19 loss-of-function variants and their potential influence on patient management within a Canadian stroke clinic population. METHODS: We randomly selected and invited outpatients attending a regional stroke prevention clinic in Toronto, Canada, who had a non-cardioembolic ischemic stroke or transient ischemic attack and were prescribed clopidogrel for secondary stroke prevention. Participants completed a self-administered home DNA test (cheek swab) to determine their CYP2C19 status. The primary outcome was the prevalence of intermediate or poor metabolizers. The secondary outcome was the proportion of participants whose antiplatelet regimen was changed as a result of the testing. RESULTS: Among 93 eligible participants who underwent the test (mean age 68.1; female 37.6%), 31 (33.3%) were intermediate metabolizers, 8 (8.6%) were poor metabolizers, 20 (21.5%) were rapid metabolizers, 9 (9.7%) were ultrarapid metabolizers and 25 (26.9%) were normal metabolizers. In 8 (100.0%) of the poor metabolizers and 20 (64.5%) of the intermediate metabolizers, treating physicians changed their antiplatelet prescriptions based on the test results. CONCLUSION: In this cohort of post-stroke patients treated with clopidogrel, genetic testing showed a high prevalence (41.9%) of intermediate or poor clopidogrel metabolizers, resulting in a change in antiplatelet therapy prescriptions in over 70% of those cases. These findings have implications for secondary stroke prevention.