Many clopidogrel patients on "inhibiting" drugs
Montreal, QC - A nationwide program in the US that makes it easy for patients on clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) to be tested for CYP2C19 polymorphisms found a fairly high proportion of patients were on concomitant drugs that inhibit enzyme activity and who thus could be at increased risk of cardiovascular (CV) events .
Dr Lon Castle (Medco Health Solutions, Franklin Lakes, NJ) 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 2011 International Congress of Human Genetics (ICHG)/2011 Annual Meeting of the American Society of Human Genetics (ASHG).
Of the first 100 patients tested between December 1, 2010 and April 30, 2011, approximately 30% of patients on clopidogrel were either 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," Castle told delegates here.
The same percentage of patients were also on a CYP2C19-inhibiting drug25% on a proton-pump inhibitor (PPI), 6% on an antidepressant, and 7% on both a PPI and an antidepressant, he added. Three months after physicians had been informed about the concomitant drugs' ability to inhibit clopidogrel metabolism, close to 40% of patients on concomitant PPI therapy had a change in their treatment regimen, physicians either discontinuing the PPI or switching to the weaker CYP2C19 inhibitor pantoprazole. Five percent actually discontinued clopidogrel.
In contrast, no change in treatment regimen was made in patients on concomitant antidepressant therapy. Pharmacy benefit organization
As Castle explained in an interview, patients covered by Medco's pharmacy benefits plan were eligible for CYP2C19 genotyping and, if interested, were provided with information on the test and a DNA 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 CV pharmacists then discuss treatment options for patients with poor metabolism phenotypes. In all, 675 physicians were offered the testing program for their patients.
Testing was most frequently offered to cardiologists (45% of all physicians), followed by primary-care physicians (approximately 35%), but surprisingly, of those offered the information, neurologists were the most likely to want to learn what the test results showed (53% of those offered), while cardiologists had the lowest acceptance rate, at approximately 30%, and primary-care physicians falling in between at approximately 42%.
Asked about the cost of the program, Castle felt that it was probably cost-neutral. "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. "But at the end of the day, if something is cost-neutral and clinically the right thing to do, I still don't think there is any reason why you shouldn't do it."
Dr Howard Levy (Johns Hopkins University, Baltimore, MD) agreed, saying 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 said in an interview.
The test also importantly identifies patients with the *17 allele who were particularly sensitive to clopidogrel and who theoretically may be at increased risk for bleeding, he added. Several novel antiplatelet agents have been approved that could be used instead of clopidogrel; however, as Levy noted, some of these drugs carry a higher risk of bleeding, at least in certain patient groups.
With clopidogrel poised to lose patent protection, the new drugs will cost considerably more. "I love the clopidogrel story, because here we have a medication that is [soon to be] available generically, so it's [going to be] inexpensive, it's got a great track record, and the majority of the population can benefit from it," 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 patients for whom it is worth the extra expense to use one of the newer drugs."