A 62-year-old male had a heart attack about 9 months ago. He was stented and placed on both aspirin 81 mg daily and clopidogrel 75 mg daily. He presents today to the emergency department and is diagnosed with a STEMI. His wife is wondering why the medications used to prevent this from happening didn’t work. Below I assess 3 possible reasons for clopidogrel failure.
ROLE OF PATIENT ADHERENCE IN CLOPIDOGREL FAILURE
Step one in any investigation about treatment failure is to assess patient adherence. When I’m dealing with a patient who is living at home and taking care of their own medications, I always put a large emphasis on adherence. This is one of the most common reasons as to why a medication doesn’t work. In addition to gently approaching (avoiding accusation) this with the patient, I would also like to get the dispensing records from the pharmacy to verify that he was routinely picking this medication up.
CLOPIDOGREL FAILURE: PHARMACOGENOMIC CONSIDERATIONS
With the growing practice of pharmacogenomics, we have to consider that this patient may have a variation of CYP2C19 that does not allow him to adequately metabolize the drug to its active form. Clopidogrel is a prodrug that requires activation by CYP2C19. This should be investigated and alternative antiplatelet therapy considered.
CYP2C19 can be affected by numerous medications. By blocking CYP2C19 action, it could result in a reduced therapeutic effect. The extent of the clinical implication of each of these drug interactions still remains debatable. However, in a patient who has had a repeat event, we must consider this possibility. I would look at the timing of new medications and dose changes. Examples of medication that could reduce the effectiveness of clopidogrel include omeprazole, cimetidine, esomeprazole, fluoxetine, fluconazole, and a list of a few other less common drugs