In patients with an initial TIA or mild CVA, the risk of recurrent stroke is approximately 3% to 5% per year, with the greatest risk during the days, weeks and months after the initial event. Clopidogrel has been shown, with and without aspirin, to reduce the risk of recurrent stroke.^1,2 Clopidogrel, however, is a pro-drug and has to be metabolized to its active form by the CYP2C19 enzymes. Carriers of CYP2C19 loss-of-function alleles do not effectively metabolize the drug, so not as much active drug is available to the body, and subsequently and there is less platelet inhibition. This has been shown to increase the risk of cardiovascular events and stent thrombosis in patients with acute coronary syndromes.³ This loss of function allele has a prevalence of up to 30% in Caucasian populations, with 2% to 3% being poor metabolizers and in patients of East Asian decent the frequency of having a loss of function allele is 50% to 60%, with 10% to 12% being poor metabolizers. In other words, the issue of poor metabolizers is common enough to be important. At this point, there is no clarity regarding whether testing for these genetic variants will yield a better outcome, but we can be certain that this will be an area where there will be a great deal of further research and eventually an area where genetic-based, personalized medicine will have a place in care. —Neil Skolnik, MD

1. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348:1329–1339. 

2. Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369:11–19. doi:10.1056/NEJMoa1215340. 

3. Mega JL, Simon T, Collet JP, et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA. 2010;304:1821–1830. doi:10.1001/jama.2010.1543.