Since the inception of this blog over 4 years ago, one of the key topics has been companion diagnostic testing for cytochrome p450 (CYP) mutations. Indeed this was the topic of the very first post.
We are now understanding that testing for at least one CYP can significantly impact patient outcomes.
CYPs are enzymes that metabolize (i.e. process and clear) pharmaceuticals, and common mutations in these enzymes can dramatically increase or decrease the rates at which drugs are metabolized. When drugs are metabolized quickly, the beneficial effects of the drugs can be significantly reduced. When drugs are metabolized slowly, the lingering presence of the drugs can introduce toxic side effects, sometimes with life or death consequences.
After cardiac patients have heart stents inserted, the standard of care includes prescribing an anti-clotting drug called clopidogrel. Clopidogrel is metabolized by a CYP called CYP2C19, and people who have mutations in the enzyme have a reduced ability to process the drug.
In a recent study, testing for CYP2C19 in heart stent patients, and prescribing an alternative anti-clotting drug for those who carried mutations, virtually eliminated the risk of follow-on adverse cardiac events. This is powerful stuff.
Over a 2 year period the research team at the University of Florida, led by Julie Johnson, PharmD, genotyped CYP2C19 in 297 heart stent patients. One third carried mutations in CYP2C19 that reduced the function of the enzyme.
Fifty-five of these mutation-carrying patients were prescribed an alternative to clopidogrel, and none of them had a major adverse event within 30 days.
Thirty-nine of the mutation-carrying patients were prescribed clopidogrel anyway, and 12.5% of them had a major cardiac event, including (according to the author) “myocardial infarction, stent thrombosis, cerebrovascular accident or CVD-related death.”
By the way, the association between CYP2C19 mutation status and cardiac risk is not new. It has been described for at least 5 years.
Point-of-care tests are now starting to crop up, but I can’t help but wonder if this remains a big opportunity for diagnostic test developers.
I know that if my loved one was about to receive a stent, I’d be damn sure to insist that CYP2C19 was tested before they got clopidogrel.