Plavix Problems with Genetic Variant Can Be Overcome with High Doses

To avoid problems where Plavix does not work in some patients, doctors could possibly use high doses of the blood thinner, according to a new report. 

According to data presented at a meeting of the American Heart Association in Orlando, Florida, tripling or quadrupling the amounts of Plavix given to patients with the CYP2C19 gene variant, which makes those individuals resistant to the drug, can overcome that resistance. The findings were published online this week by the Journal of the American Medical Association.

Researchers looked at 335 patients who had suffered a heart attack and found that they were able to overcome the inability of some patients to metabolize Plavix due to genetics with much larger doses. The method worked in all but 10% of patients with the gene variant, and resulted in no additional risk of Plavix side effects, researchers reported.

Plavix (clopidogrel) is a blood thinner that prevents blood platelets from sticking together to form clots. It is a blockbuster medication, generating annual sales of over $6 billion for Bristol Myers Squibb Co. and Sanofi-Aventis.

In August 2009, researchers from the University of Maryland identified a gene variant found in about one-third of the population that may signal a reduced effectiveness of Plavix.

People with the CYP2C19 variant have reduced functioning of a liver enzyme that is supposed to convert Plavix from its inactive form to its active form, potentially making Plavix ineffective at reducing the risk of blood clots.

There are between 2.5 million and 3 million Plavix prescriptions handed out each month in the U.S., and doctors have been debating what to do about patients who are geneticailly predisposed toward Plavix resistance.

The debate started after the FDA announced a new Plavix black box warning in March 2010, alerting doctors and patients about the risk of serious or potentially life-threatening injuries that could be suffered by individuals who are poor metabolizers of Plavix, rendering the drug ineffective.

The findings come as the patent on Plavix runs out next year, opening the door to generic versions that will probably cause the cost of Plavix to bottom out. Plavix also faces competition from new blood thinners like Eli Lilly’s Effient and AstraZeneca’s Brilinta.

A number of Plavix lawsuits have been filed against the manufacturers alleging that the makers of Plavix promoted the expensive medication as a safer alternative to aspirin, although it may actually provide no benefit over taking a four-cent-a-day aspirin. Plaintiffs allege that they suffered injuries as a result of their unnecessary use of Plavix, such as gastrointestinal bleeding, severe ulcers, heart attacks, strokes and a rare blood disorder known as TTP, or thrombotic thrombocytopenic purpora.

Plaintiffs allege that the drug makers repeatedly overstated the safety and effectiveness of Plavix, and point out that the companies were repeatedly cited by the FDA for illegal, off-label promotions and for ads and campaigns that touted its benefits over aspirin and how safe it was for the stomach; both claims that the FDA said were unproven, and that several scientific studies brought into doubt.