FRANKLIN LAKES, N.J., Nov. 11, 2008 — Medco HealthÃ‚Â Solutions, Inc. (NYSE: MHS) today presented a study at the 2008 ScientificÃ‚Â Sessions of the American Heart Association that showed an increased riskÃ‚Â for major cardiovascular events in patients taking clopidogrel (the activeÃ‚Â ingredient in Plavix) and proton pump inhibitors (PPIs) together.
In the largest study of its kind to date, researchers at Medco reportÃ‚Â that PPIs inhibit the effectiveness of clopidogrel, the number twoÃ‚Â prescription drug in the world, thus increasing the risk of a major cardiac
event, such as heart attacks and strokes by 50 percent. Since PPIs mimicÃ‚Â the effect of a variant gene, which also renders clopidogrel ineffective,Ã‚Â this study further suggests a potential role for genetic testing.
“Considering the widespread use of these two medications, thisÃ‚Â important research adds to a growing body of evidence raising questionsÃ‚Â about their concurrent use and suggests further research is needed,” saidÃ‚Â Dr. Robert Epstein, a lead study author, chief medical officer, Medco.Ã‚Â “With this research in hand, we intend to open a dialogue with the majorÃ‚Â clinical organizations to advance the discussion around the guidelines that
govern the use of Plavix.”
Researchers tracked 16,690 patients who had undergone a percutaneousÃ‚Â coronary intervention such as stent placement or balloon angioplasty, andÃ‚Â had started taken clopidogrel as maintenance therapy. Of the patients inÃ‚Â the study, 9,862 patients were taking clopidogrel alone; and 6,828 patientsÃ‚Â were taking clopidogrel and a PPI. Researchers tracked the two groups inÃ‚Â the study for a 12-month period using medical and pharmacy claims data.
Results of the study were striking: researchers reported that theÃ‚Â relative risk of a major adverse cardiovascular event was 50 percentÃ‚Â higher, and the relative risk of a heart attack specifically was 74 percentÃ‚Â higher, in patients taking both medications together. The incidence of aÃ‚Â major cardiovascular event within 12 months of starting clopidogrel was 25Ã‚Â percent for patients taking both medications concurrently. The study wasÃ‚Â funded solely by Medco.
Genetic variability and clopidogrel:
For clopidogrel to work, it must first be converted to its active formÃ‚Â by a liver enzyme called cytochrome P450 2C19. PPIs interfere with thisÃ‚Â enzyme reducing the amount of clopidogrel that is converted to an activeÃ‚Â form. The gene that produces this enzyme can vary such that individuals canÃ‚Â have more or less enzyme activity, thus affecting its functionality. TheÃ‚Â way PPIs interfere with the conversion of clopidogrel to an active form mayÃ‚Â mimic this genetic variation that produces lower amounts of the enzyme,Ã‚Â suggesting that genetic testing for this enzyme may be useful. OtherÃ‚Â studies have shown that as many as 30 percent of people worldwide are bornÃ‚Â with this particular genetic variation.
Alerting physicians to potential risk for patients
Based upon this and other research on the issue, Medco will beginÃ‚Â alerting prescribing physicians through a range of communications via itsÃ‚Â Medco Therapeutic Resource Centers (R) and other channels so thatÃ‚Â prescribers can reconsider the risk/benefit of concurrent prescribing ofÃ‚Â clopidogrel and PPIs based on their patients individual circumstances.
Medco will also communicate its findings to various clinicalÃ‚Â organizations to encourage continued dialogue around prescribing guidelinesÃ‚Â for these two medications. Medco’s researchers plan to provide the findingsÃ‚Â to the Food and Drug Administration (FDA) as part of their recentlyÃ‚Â announced research collaboration in the area of pharmacogenomics.