By Kathleen Doheny
WebMD Health News
Reviewed by Brunilda Nazario, MD
July 25, 2014 -- When the blood-thinner drug Pradaxa (dabigatran) was FDA-approved in 2010 to prevent stroke in people at high risk, a major selling point was that it doesn't require frequent blood tests like the old standby drug, warfarin.
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Now, an investigation in the BMJ has raised concerns again about this newer-generation blood thinner, or anticoagulant. Doctors might prevent serious bleeding, a potential side effect of all anticoagulants, by checking the blood levels of people on Pradaxa, these experts say.
In the report, published Wednesday, experts argue that the guidelines for using Pradaxa could be flawed. Those who approved it did not see drug company information showing that testing blood levels of the drug could reduce major bleeding problems greatly, the experts say.
In response, Boehringer Ingelheim, the drug maker, issued a statement, reassuring those who take the drug that it is safe and effective as it is now used.
WebMD turned to experts, the FDA, and Boehringer Ingelheim to explain further.
How does Pradaxa compare to warfarin, the drug used for years to lower stroke risk?
Blood thinners work to prevent strokes by keeping the blood thin enough to prevent clots. If the blood becomes too thin, the risk is serious bleeding.
According to the FDA, Pradaxa -- as well as two others new oral blood-thinners, Xarelto (rivaroxaban) and Eliquis (apixaban) -- were found either equal to or better than warfarin at preventing strokes. The drugs were approved based on clinical trials including more than 50,000 patients, the FDA says.
More than 850,000 patients have been prescribed Pradaxa since its approval, according to Boehringer Ingelheim.
A typical dose of Pradaxa costs about $300 a month, compared to $4 a month for a typical dose of generic warfarin.
What are the major concerns raised in this investigation about Pradaxa?
Safety is the major one, says Thomas J. Moore, senior scientist at the Institute for Safe Medication Practices. He wrote an analysis to accompany the investigation.
Any anticoagulant treatment carries risks, he says. "Anticoagulant treatment for people with atrial fibrillation ranks as one of the highest-risk treatments in older Americans," he says. More than 15% of older patients treated for atrial fibrillation with blood thinners for 1 year have bleeding, he says.
Concerns about Pradaxa surfaced 2 years ago, he says, when doctors began reporting a larger number of serious and sometimes fatal bleeding problems in older patients on the drug.
The claim by the company that the drug needs no blood-level monitoring is misguided, Moore says. "It turns out the company has had data for several years, showing the amount of anticoagulation [blood thinning] varied [from patient to patient] more than five-fold."
That means, Moore says, that "the same dose could produce widely varying effects on blood clotting. Some patients would be at extremely high risk of bleeding. Others would not get a strong enough blood clotting effect to serve its purpose, reduce the risk of stroke."
According to the BMJ report, the company re-analyzed drug information in 2012, finding that blood-level monitoring and adjusting the dose could lower major bleeding problems by 30% or 40% compared to warfarin -- but regulators and doctors weren't informed, the report says. The company refutes this.
"The concerns are that Pradaxa was approved on the basis that it did not require monitoring," says Rita Redberg, MD, MSc, a professor of medicine at the University of California, San Francisco. Redberg wrote an editorial to accompany the analysis. "There is now new evidence that has come to light suggesting it is not safe to use it without monitoring, particularly in the elderly and those with kidney failure. The bleeding risk is higher than we first thought and the effectiveness is basically equivalent to warfarin.''
What's needed, Moore says, is for doctors to pinpoint a patient's ideal blood level and regularly check it.
What does the drug maker say?
In a press release issued in response to the report, Boehringer Ingelheim says it did study the effect of blood-level testing and dose adjusting and concluded it was not needed.
"The truth is the totality of scientific evidence does not support dosing decisions for Pradaxa based on blood levels," the statement reads in part.
Other factors, such as how well the kidneys work, affect the risk of bleeding, too, the company says.
What does the FDA say about Pradaxa?
"At this time, FDA continues to believe that Pradaxa provides an important health benefit when used as directed and recommends that health care professionals who prescribe Pradaxa follow the recommendation in the approved drug label," says Sandy Walsh, an FDA spokesperson, in an email.
The agency still thinks the drug's benefits outweigh the risks, she says.
What do experts say patients should do now?
People on the drug should ask their doctors about their individual risks and benefits, Redberg says.
"At this time, I think we should stay with what we know works, and that is warfarin," she says.
If you take an anticoagulant, don't stop taking it without talking to your doctor. Stopping it can raise your stroke risk.
SOURCES: Rita Redberg, MD, MSc, cardiologist and professor of medicine, University of California San Francisco Medical Center. Thomas J. Moore, senior scientist, Institute for Safe Medication Practices. Sandy Walsh, FDA spokesperson. Cohen, D. The BMJ, July 23, 2014. Press release, Boehringer Ingelheim.
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