Genetic Testing in Patients Undergoing PCI
PracticeUpdate: Could you describe the rationale and any clinically relevant outcomes for the PHARMCLO and ADAPT trials?
Dr. Bhatt: Genetic testing in general with respect to antiplatelet therapy is not widespread, but at certain centers it does occur. There's been a lot of research that’s gone on including the two recent trials presented at ACC. There's certainly some signals here that genetic testing may help us modify antiplatelet therapy, so-called tailoring antiplatelet therapy, the results are certainly provocative, though I think we still do need more data before any of this being actionable.
PracticeUpdate: What is the current state of genetic testing for the personalized selection of antiplatelet therapy in patients undergoing PCI?
Dr. Bhatt: Personalizing antiplatelet therapy is allottable goal, and several attempts have been made. Platelet function testing has been utilized in the context of randomized clinical trials to decide on the optimal antiplatelet cocktail, both duration and intensity, for patients undergoing stenting and even in some cases more broadly with acute coronary syndromes. The results are a bit mixed. Largely, I would say the majority of studies have not demonstrated clear cut benefit of an approach of platelet function testing.
The hope is with genetic testing, which in some respects is more precise because if, for example, someone is a homozygote for CYP2C19 reduced functional alleles, they're not going to produce a lot of clopidogrel metabolites, so if one is using clopidogrel, potentially that homozygote may not have a therapeutic level of active metabolite of that drug, so in that sort of circumstance, theoretically, genetic testing seems like it should be useful.
That’s not been so easy to prove and the data have been quite mixed, whether genetic testing does anything more than predicts risks, does it actually provide information that’s actionable, and we do have some emerging data that it might be actionable, but I'm really waiting for more data, larger studies, more confirmatory trials, for example, the TAILOR-PCI trial that the Mayo Clinic is running and now, in fact, have partnered with the National Institutes of Health would provide a large amount of information about whether genetic testing is useful to actually guide therapy, i.e. clopidogrel versus ticagrelor or choice.
PracticeUpdate: How do you see genetic testing in PCI patients being integrated into clinical practice in the near future?
Dr. Bhatt: I suspect in the future genetic testing will become more common for a variety of diseases, and in that context, I suspect genetic testing for various polymorphisms associated with quote on quote clopidogrel resistance will also become more common. Right now, I wouldn't really recommend any of that sort of testing for its own sake. I think we need more data helping us decide what to do with that information. The real question isn’t so much whether it determines elevated risks that it appears to but rather is it modifiable risk, is there something we can do different with that knowledge.
Otherwise, I'm not sure there's value in just getting a test for its own sake, but having said that, I do suspect once the price of genetic testing comes down enough, patients might have a situation where much of their genetic information is already in the medical record even before a question of whether they have antiplatelet resistance or not comes up, so the information might be there anyway and then, it would be hard not to at least look, but until we enter that era of widespread genetic testing, for the time being, I’d say wait until the ongoing trials of personalized antiplatelet therapy with genetic testing are complete, and depending on what they show maybe change practice, but until then, I wouldn't.
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