Medco Research Institute announced this week that it is sponsoring a study to determine the optimal antiplatelet treatment for patients who are also using a proton pump inhibitor for the treatment of heartburn. The study will involve genetic testing to establish which patients can respond to Plavix.
The study will examine the impact that the PPI Prevacid has on patients' ability to metabolize two antiplatelet agents, Effient and a double dose of Plavix. In the study, researchers will also genetically test patients to see if they harbor mutations hindering Plavix metabolism.
“What we already know is that the benefits of [Bristol-Myers Squibb's] Plavix can be blunted either by genetics or the use of second drugs like a proton pump inhibitor,” said Robert Epstein, Medco’s chief medical officer and president of the Medco Research Institute, in a statement. “What we hope to learn from this study is whether you can avoid this problem through double dosing Plavix or whether you need to move on to newer drugs like Effient."
According to Epstein, the findings of this study will have clinical and economic implications, since Plavix is expected go off patent in 2012. According to reports, Eli Lilly and Daiichi Sankyo have priced Effient at an 18 percent premium to Plavix's current price.
The study, which is slated for completion by year end, is the first head-to-head trial investigating the impact of a heartburn treatment on anti-platelet drugs, Medco said. The pharmacy-benefit manager is working with researchers at Pitie-Salpetriere Hospital in Paris, a leading cardiovascular research center, to conduct the study.
PPIs are commonly prescribed with antiplatelet agents to prevent gastrointestinal bleeding, but have been shown to blunt the clinical benefit of Plavix and raise the risk of a major adverse cardiovascular event, such as a stroke or heart attack, by 50 percent in patients using both drugs together.
"The study aims to determine if Prevacid would be less likely to impair the efficacy of Plavix taken at a double dose (150 mg) per day and contrast that result with Effient, a newer, costlier drug found to be more effective but with a greater bleeding risk than Plavix," Medco said in a statement. Plavix and Effient are currently marketed to prevent cardiovascular death, myocardial infarction, and stroke in patients who have had a recent heart attack or acute coronary syndrome with or without a stent.
In conducting the study, Ascopharm Groupe Novasco will manage the 104-patient study for the Medco Research Institute. The patients will be divided into two groups, one receiving Effient and the other receiving 150 mg per day Plavix. Then each arm will be randomized to receive either Prevacid or placebo.
Researchers, led by Jean-Sebastien Hulot, will measure the antiplatelet effect of the medications in each group at the start of the study and two weeks after patients have been receiving the PPI. All patients in the study will take a genetic test to predict Plavix metabolism, which is expected to further elucidate the interplay of genes in response to anti-platelet drugs.
Previously, Medco’s conducted the Clopidogrel Medco Outcomes Study, which was published last year in Pharmacotherapy and reported that the use of a PPI in conjunction with Plavix increases patients' risk of hospitalization for a cardiovascular event by 51 percent over a 12-month period.
According to Medco, the new study could lay the groundwork for additional collaborative research efforts in the field of personalized medicine.
Medco Research Institute has also launched a head-to-head trial of Plavix and Effient measuring the impact of genes in patient response to these drugs (PGx Reporter 10/21/2009). That study will examine whether the 70 percent to 75 percent of patients who are "extensive metabolizers" of Plavix have similar outcomes to patients taking Effient. The study is slated for completion in 2012, when Plavix is expected to lose patent protection and face generic competition.
Precisely because it's going off patent, Plavix is a perfect candidate for Medco's Genetics for Generics program, an effort launched by the PBM to apply genetic testing to lower the cost of healthcare for its customers. Furthermore, the label for Plavix was recently updated by the US Food and Drug Administration to inform doctors and patients that poor CYP2C19 metabolizers have diminished response to the drug and are at increased risk for heart attacks (PGx Reporter 06/17/2009).