Pam Harrison

October 18, 2011

October 18, 2011 (Montreal, Quebec) — A nationwide program that makes it easy for patients taking clopidogrel to be tested for CYP2C19 polymorphisms found that a fairly high proportion of them were taking concomitant dugs that inhibit enzyme activity, putting them at increased risk for cardiovascular events.

Lon Castle, MD, senior director of clinical innovations and personalized medicine at Medco Health Solutions, Franklin Lakes, New Jersey, and colleagues assessed the uptake and impact of a personalized medicine program that informs physicians and patients about the value of CYP2C19 genotyping and facilitates access to that testing. They reported their findings here at the 12th International Congress of Human Genetics and the 61st American Society of Human Genetics Annual Meeting.

Of the first 100 patients tested between December 1, 2010 and April 30, 2011, approximately 30% of those taking clopidogrel were poor or intermediate metabolizers; 37% were extensive metabolizers, and 33% were ultrarapid metabolizers. "Some 38% of patients had the *17 allele, and thus could be at greater bleeding risk," Dr. Castle told delegates.

The same percentage of patients was also taking a CYP2C19-inhibiting drug — 25%, a proton pump inhibitor (PPI); 6%, an antidepressant; and 7%, both, he added. Three months after physicians had been informed about the concomitant drugs' ability to inhibit clopidogrel metabolism, close to 40% of patients taking concomitant PPI therapy had a change in their treatment regimen, either discontinuing the PPI or switching to the weaker CYP2C19 inhibitor pantoprazole (5% actually discontinued clopidogrel).

In contrast, no change in treatment regimen was made in patients taking concomitant antidepressant therapy.

Pharmacy Benefit Organization

As Dr. Castle explained to Medscape Medical News, Medco Health Solutions is a pharmacy benefit organization that manages outpatient medications for approximately 65 million people in the United States. Medco clients pay for their medications with a special card and, once managers receive prescribing information, "we can reach out to physicians, inform then about the test, and ask them if that might be something they are interested in for their patients," Dr. Castle explained.

If the physician indicates that they are interested in having their patient tested, patients are educated about the value of CYP2C19 genotyping and provided with a DNA sample collection kit. DNA is then genotyped for alleles 1 to 8, as well as the *17 allele. This information, together with metabolism phenotype and a list of medications that inhibit CYP2C19, are reported to physicians. Specially trained cardiovascular pharmacists then discuss treatment options for patients with poor-metabolism phenotypes.

As initial analyses showed, cardiologists were most frequently offered testing (45% of all physicians), perhaps not surprisingly, followed by primary care physicians (approximately 35%). Neurologists had the highest acceptance rate for CYP2C19 testing (approximately 53%), whereas cardiologists had the lowest acceptance rate (approximately 30%); primary care physicians fell between neurologists and cardiologists (approximately 42%).

When asked about cost, Dr. Castle said: "By the time you figure in the cost of the test and the cost of administering the program to physicians and to patients, it's probably cost-neutral," he said. "At the end of the day, if something is cost-neutral and clinically the right thing to do, I don't think there is any reason you shouldn't do it."

Howard Levy, MD, PhD, from the division of general internal medicine and McKusick-Nathan Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland, agrees that offering patients the CYP2C19 genotype test is "absolutely" the right thing to do.

"If you are going to go to the trouble of putting patients on medications that we hope will make them better, it would be nice to know that we are indeed making them better, or at least not making them worse," he told Medscape Medical News.

The test also identifies patients with the *17 allele, who are more efficient at activating clopidogrel and who theoretically might be at increased risk for bleeding, he added. Several novel antiplatelet agents have been approved that could be used instead of clopidogrel. However, Dr. Levy noted, these drugs carry a higher risk for bleeding, at least in certain patient groups.

Now that clopidogrel [will soon be] available generically, those other agents also cost considerably more than clopidogrel. "I love the clopidogrel story: We have a medication that is [nearly] available generically, so it's inexpensive, it's got a great track record, and the majority of the population can benefit from it," Dr. Levy said. "But for patients who are on an inhibiting drug, or for those who are genetically not able to activate clopidogrel and who won't benefit from it as much, we now have a tool to identify those for whom it is worth the extra expense to use one of the newer drugs."

Dr. Castle is an employee of Medco Health Solutions. Dr. Levy has disclosed no relevant financial relationships.

12th International Congress of Human Genetics (ICHG) and the 61st American Society of Human Genetics (ASHG) Annual Meeting: Abstract 149. Presented October 13, 2011.


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