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New study: A Common Class of GI Medications Reduce Protection Against Heart Attack in Patients Taking Widely Prescribed Cardiovascular Drug

Proton Pump Inhibitors increase risk of major cardiovascular event by more

than 50 percent for patients taking Plavix(R)

Study may anticipate a role for genetic testing in association with

clopidogrel prescribing

FRANKLIN LAKES, N.J., Nov. 11 /PRNewswire-FirstCall/ -- Medco Health Solutions, Inc. (NYSE: MHS) today presented a study at the 2008 Scientific Sessions of the American Heart Association that showed an increased risk for major cardiovascular events in patients taking clopidogrel (the active ingredient in Plavix) and proton pump inhibitors (PPIs) together.

In the largest study of its kind to date, researchers at Medco report that PPIs inhibit the effectiveness of clopidogrel, the number two 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 mimic the effect of a variant gene, which also renders clopidogrel ineffective, this study further suggests a potential role for genetic testing.

"Considering the widespread use of these two medications, this important research adds to a growing body of evidence raising questions about their concurrent use and suggests further research is needed," said Dr. Robert Epstein, a lead study author, chief medical officer, Medco. "With this research in hand, we intend to open a dialogue with the major clinical organizations to advance the discussion around the guidelines that govern the use of Plavix."

Study details

Researchers tracked 16,690 patients who had undergone a percutaneous coronary intervention such as stent placement or balloon angioplasty, and had started taken clopidogrel as maintenance therapy. Of the patients in the study, 9,862 patients were taking clopidogrel alone; and 6,828 patients were taking clopidogrel and a PPI. Researchers tracked the two groups in the study for a 12-month period using medical and pharmacy claims data.

Results of the study were striking: researchers reported that the relative risk of a major adverse cardiovascular event was 50 percent higher, and the relative risk of a heart attack specifically was 74 percent higher, in patients taking both medications together. The incidence of a major cardiovascular event within 12 months of starting clopidogrel was 25 percent for patients taking both medications concurrently. The study was funded solely by Medco.

Genetic variability and clopidogrel:

For clopidogrel to work, it must first be converted to its active form by a liver enzyme called cytochrome P450 2C19. PPIs interfere with this enzyme reducing the amount of clopidogrel that is converted to an active form. The gene that produces this enzyme can vary such that individuals can have more or less enzyme activity, thus affecting its functionality. The way PPIs interfere with the conversion of clopidogrel to an active form may mimic this genetic variation that produces lower amounts of the enzyme, suggesting that genetic testing for this enzyme may be useful. Other studies have shown that as many as 30 percent of people worldwide are born with this particular genetic variation.

Alerting physicians to potential risk for patients

Based upon this and other research on the issue, Medco will begin alerting prescribing physicians through a range of communications via its Medco Therapeutic Resource Centers (R) and other channels so that prescribers can reconsider the risk/benefit of concurrent prescribing of clopidogrel and PPIs based on their patients individual circumstances.

Medco will also communicate its findings to various clinical organizations to encourage continued dialogue around prescribing guidelines for these two medications. Medco's researchers plan to provide the findings to the Food and Drug Administration (FDA) as part of their recently announced research collaboration in the area of pharmacogenomics.

About Medco

Medco Health Solutions, Inc. (NYSE: MHS) is the nation's leading pharmacy benefit manager based on its 2007 total net revenues of more than $44 billion. Medco's prescription drug benefit programs, covering approximately one-in-five Americans, are designed to drive down the cost of pharmacy health care for private and public employers, health plans, labor unions and government agencies of all sizes, for individuals served by the Medicare Part D Prescription Drug Program, and those served by Medco's specialty pharmacy segment, Accredo Health Group. Medco, the world's most advanced pharmacy(R), is positioned to serve the unique needs of patients with chronic and complex conditions through its Medco Therapeutic Resource Centers(R), including its enhanced diabetes pharmacy care practice through the Liberty acquisition. Medco is the highest-ranked independent pharmacy benefit manager on the 2008 Fortune 100 list. On the Net:

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that may cause results to differ materially from those set forth in the statements. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. We undertake no obligation to publicly update any forward- looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the risks and uncertainties that affect our business, particularly those mentioned in the Risk Factors section of the Company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission.

SOURCE Medco Health Solutions, Inc.
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