In a step toward filling an unmet medical need, an experimental drug completely reversed the blood-thinning effects of the anticoagulant Pradaxa "within minutes" of being given, according to early results from a international study.
Pradaxa, or dabigatran, is among four newer anticoagulants prescribed to people with a common abnormal heart rhythm that puts them at risk of blood clots leading to stroke.
While the novel pills do not require continual, inconvenient testing of blood levels like the age-old anticoagulant warfarin, they do not have an antidote to undo their effect in an emergency. Warfarin can be reversed with a shot of vitamin K.
The new study, sponsored by Pradaxa maker Boehringer Ingelheim and published online Monday in New England Journal of Medicine, is being led by Charles Pollack, chair of emergency medicine at Pennsylvania Hospital.
The experimental drug, called idarucizumab, binds to Pradaxa, neutralizing its activity. In small previous studies of healthy volunteers, the reversal effects were immediate and restored normal blood clotting. Importantly, it did not have a procoagulant effect, meaning it did not promote clotting.
The ongoing study, which aims to treat 300 patients, is being conducted at hundreds of hospitals in 38 countries. It is designed to see how well idarucizumab works in real-life emergencies - when patients suddenly need surgery, or when they are suffering life-threatening bleeding as a result of anticoagulation. While rare, such dangerous bleeding happens in about 1.5 percent of patients on Pradaxa per year. (Pradaxa is cleared from the body within a day, so a reversal drug would not be needed for patients who can wait a day or more for surgery.)
The latest results are from 51 patients who had bleeding in their brains or other organs, and 39 who urgently needed surgery because ofinjuries or complications of chronic medical conditions.
Within minutes of getting a rapid intravenous infusion or a shot of idarucizumab, tests of clotting factors showed it "completely reversed the anticoagulant effect" of Pradaxa and restored normal blood clotting, the study found.
However, the patients - average age 77 - were still critically ill. Some with hemorrhages took 11 hours or more to stop bleeding. A total of 18 patients died.
Imagine that a patient taking Pradaxa gets in a car crash, said study leader Pollack, who has no financial interest in the drug.
"The effect of dabigatran is gone within minutes" of getting the reversal agent, said Pollack, who next month will become associate provost at Thomas Jefferson University. "However, he's got a hole in his chest, holes in his blood vessels. This takes anticoagulantion off my list of concerns, but that's just one part of the problems that the patient is facing."
Peter R Kowey, chief of cardiovascular diseases at Lankenau Heart Institute, echoed that sentiment.
"The data are very clean; the drug clearly works," said Kowey, who is not part of the study. "But everybody has to be clear that if a catastrophic event occurs, simply reversing the effect of anticoagulation may not be not enough. Patients still face a high mortality rate."
More than 2 million Americans have atrial fibrillation, the abnormal heart rhythm that puts them at risk of stroke. Pradaxa and the other novel anticoagulants (Eliquis, Savaysa and Xarelto) are relatively pricey.
Pradaxa, for example, costs $315 a month, compared to about $16 for warfarin. But warfarin also involves the costs of monitoring to keep it within a safe range.
Although other anticoagulant reversal agents are in development, Boehringer's is in the lead. In April, the U.S. Food and Drug Administration said it would give accelerated review to idarucizumab's application when the current study is complete. Boehringer officials said they can't predict when that will be because hospitals are still joining the study.