A recent report questions whether more could be done to prevent side-effects and improve effectiveness of the anti-clotting drug dabigatran, but medical experts urge people to continue taking the medication as prescribed unless their physician says otherwise.
The drug, sold under the brand name Pradaxa, is one of a relatively new class of anti-clotting drugs and is prescribed to people with atrial fibrillation to help prevent stroke. Atrial fibrillation is an irregular heart rhythm that increases the risk of stroke.
“It is essential that people know that they should not change or stop any of this type of drug without talking to their doctor,” said Rose Marie Robertson, M.D., chief science and medical officer for the American Heart Association. “Reports come out often about drugs, but your own healthcare provider is your best source of treatment information. In this particular case, missing even one or two doses of dabigatran without substituting another medication to fight clotting can leave you unprotected from stroke.”
The British Medical Journal released a report Wednesday that questions whether drugmaker Boehringer-Ingelheim fully disclosed all it knew about potential ways to lower the risk of the bleeding side effects of Pradaxa, involving measuring the blood levels or anti-clotting effects in individual patients. The company criticized the journal’s story as misleading and inaccurate.
Dabigatran was approved by the Food and Drug Administration in 2010, largely based on a large clinical trial that found it was as effective as the standard drug used, warfarin, and the concept that patients would not need to have blood drawn for regular monitoring of effectiveness, as is done with warfarin.
As with all anti-clotting drugs, including warfarin, dabigatran can cause gastrointestinal, brain or other bleeding. And even with the drug, there still remains some residual risk of stroke.
Warfarin has been used to treat atrial fibrillation patients since the 1950s and is a less costly drug. It requires frequent, usually monthly, blood monitoring to adjust the dosage given.
Dan Roden, M.D., assistant vice-chancellor for personalized medicine at Vanderbilt University and a leading expert in pharmacology, noted that the process of developing new drugs is long and complicated.
“The drug development and evaluation process is complex and always involves an assessment of risk and benefit, often across multiple population subtypes,” said Roden, who is also an American Heart Association volunteer. “Warfarin, a drug we know well, has the drawbacks of a need for frequent monitoring and the potential for drug and food interactions, and therefore the pharmaceutical industry has tried to develop new agents to avoid these issues.”
The clinical trial of dabigatran, known as the RE-LY trial, found that bleeding could also occur with Pradaxa. But that report and a subsequent analysis found there was no greater bleeding risk than with warfarin.
The report in the British Medical Journal says company documents were not provided to physicians and regulators that found that blood level monitoring and dose adjustment might reduce major bleeding significantly. The blood test used in those analyses has not currently been approved for use in the United States.
Boehringer-Ingelheim said no monitoring was needed with the drug, and also said in a news release that it had provided regulators with all data. The company cited regulators’ conclusion that there is “an important health benefit when used as directed.”
The issue of monitoring is important for many people, Roden said.
“For some patients, an ability to forego monitoring may represent a sufficiently large benefit that it outweighs the risk,” he said. “However, while we use many medications without monitoring drug levels in the blood or assays of drug effect, we surely understand that ‘one size fits all’ is an approach that will necessarily result in less efficacy and greater risk across a population.”
In 2011, the American College of Cardiology, the American Heart Association and the Heart Rhythm Society recommended dabigatran, among other drugs in this class, as an alternative to warfarin.
The drug also has been approved by the European Medicine Agency and the Canadian Cardiovascular Society. As further published research becomes available, or if specific action is taken by the FDA, the American Heart Association and American Stroke Association will include it in their ongoing evaluation of recommendations for dabigatran and other such drugs.
For more information:
- Questions about using dabigatran
- Atrial fibrillation treatment guidelines
- Atrial fibrillation medications
Boehringer Ingelheim provides financial support to the American Heart Association, a nonprofit organization that relies on contributions from individuals, corporations, foundations and other organizations to fight heart disease and stroke. Boehringer Ingelheim is the AHA’s largest pharmaceutical donor, although that support makes up a small percentage of annual donations. Revenues from pharmaceutical companies, device manufacturers and health insurance providers represented approximately 2 percent of revenue in the last fiscal year. The AHA has strict policies to prevent these relationships from influencing the AHA’s science content. Detailed financial and donation information can be found here.