Clinical Geriatrics

To the Editor,
I generally agreed with the analysis and conclusions of the article in the January 2010 edition of Clinical Geriatrics entitled “Appropriate Use of Clopidogrel in the Older Adult” by Dr. Ackermann.1 I have two comments:

1. I think the potential for drug-drug interactions at the cytochrome P450 2C19 enzyme should be emphasized more. Dr. Ackermann mentions the potential interaction of proton pump inhibitors (PPIs) with clopidogrel. These drugs are common in the elderly, and I doubt many primary care physicians or specialists who prescribe clopidogrel even consider this interaction. Perhaps the worst offender of PPIs is omeprazole, which is over the counter, and many patients may be taking it without their physicians’ knowledge. With clopidogrel being a prodrug needing 2C19 activity, it would render the clopidogrel less effective or perhaps useless. In this sense, the drug-drug interaction is a “silent” one—no obvious adverse drug reaction occurs. And if a patient has a cardiovascular event, it will not likely be attributed to the drug-drug interaction since patients who go on antiplatelet therapy still have cardiovascular events. In addition, other common drugs may have this interaction as well, such as fluoxetine.

2. The cost of testing for cytochrome P450 2C19 alleles is not expensive. Several labs can do this testing for $100-200, and it is reimbursable, in my experience, through most insurance and Medicare if properly justified. The study by Mega et al2 showed that carriers of one inactive allele had reduced active blood levels of active metabolite of clopidogrel, and, more importantly, had “a relative increase of 53% in the composite primary efficacy outcome of the risk of death from cardiovascular causes, myocardial infarction, or stroke, as compared with noncarriers (12.1% vs 8.0%; hazard ratio for carriers, 1.53; 95% confidence interval [CI] = 1.07-2.19; P = 0.01) and an increase by a factor of 3 in the risk of stent thrombosis (2.6% vs 0.8%; hazard ratio, 3.09; 95% CI= 1.19-8.00; P = 0.02).” The results of those who would have both alleles dysfunctional likely would be worse. It is estimated that 2-6% of Caucasians have both alleles dysfunctional, as do 10-20% of Japanese and African-American persons.3 Those with one functional allele represent approximately 30% of the population. It would seem prudent to consider genetic testing before or at the time of starting clopidogrel, and then re-evaluating its usefulness once the results are returned.

Scott C. Armstrong, MD
Medical Director, Tuality Center for Geriatric Psychiatry
Forest Grove, OR
Associate Clinical Professor of Psychiatry
Oregon Health & Science University, Portland

Dr. Armstrong reports no relevant financial relationships.

References

1. Ackermann R. Appropriate use of clopidogrel in the older adult. Clinical Geriatrics 2010;18(1):41-47.

2. Mega JL, Close SL, Wiviott SD, et al. Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med 2009;360:354-362.

3. Clopidogrel (Plavix) DNA Test-CYP2C19. Genelex Website. http://www.healthanddna.com/drug-safety-dna-testing/clopidogrel.html. Accessed March 1, 2010.