Clopidogrel Failure: Why Did I Have Another Heart Attack?

heart failure

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.

Drug Interaction

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 found here.

What did I miss and what else might you consider reviewing in the patient scenario?

Here’s another case that might interest you of antibiotic failure due to a drug interaction.

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Written By Eric Christianson

August 21, 2019

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