Plavix warning may not be necessary

The popular blood thinner Plavix is a safe and effective medication for patients, including those deemed to be "poor metabolizers" of the drug, according to an analysis released Tuesday in the Journal of the American Medical Association.

The findings contradict the 2010 boxed warning that the U.S. Food and Drug Administration mandated on the drug's label.

If you're one of the approximately 40 million people worldwide taking Plavix (known generically as clopidogrel), you're probably familiar with the warning. The label cautions that the drug has "diminished effectiveness in poor metabolizers" or patients with a certain genotype, known as CYP2C19, and thus may lead to an increase in cardiovascular events like heart disease or bleeding. To help decide whether Plavix is a good fit for patients, the label says genetic tests are available to identify people with the genotype in question.

Yet in the analysis published Tuesday, researchers looked at 32 studies, involving more than 42,000 patients, and concluded that Plavix works well in patients both with and without the genotype. They found no significant increase in cardiovascular events in patients with the genotype who took Plavix.

"The drug Plavix itself is not active, it has to be metabolized in order to become activated," said Dr. Steven Nissen who is with the department of cardiovascular medicine at The Cleveland Clinic. The liver enzyme CYP2C19 is what activates the drug.

"If you're a slow metabolizer theoretically you might not produce enough active drug to get the anti-coagulant effect of Plavix and that's why all of this from a theoretical point of view made sense. But the problem is that theory is one thing, but reality is another."

Nissen was not affiliated with the analysis but wrote an editorial accompanying its publication. He believes that the FDA jumped the gun in mandating the boxed warning.

"FDA acted prematurely in putting a warning on the drug without the level of evidence that we would consider to be adequate for most standards," said Nissen.  "They were trying to do the right thing but if you look at it in the most rigorous fashion, it wasn't the right answer and it's now time to rethink it."

In a written statement to CNN, a FDA spokesperson said the agency did not have a specific comment on the analysis.

"Generally, we do not provide comments on individual studies, reports or articles. Rather, the FDA collectively reviews the literature and takes such information into account as we discuss drug safety issues and make regulatory decisions."

So what does this new information mean for patients?

Nissen says patients taking Plavix should not be concerned about not being able to metabolize the drug.  He said that poor metabolizers "appear to have no difference in outcome; they don't have any more strokes, heart attacks, or deaths when they take the drug than people who are good metabolizers."