Death magnifies Pradaxa hemorrhage concerns
Tue Mar 6, 2012 10:40pm EST
March 6 (Reuters) – The death of an elderly man from a massive brain hemorrhage after a routine fall suggests that bleeding complications from Boehringer Ingelheim's Pradaxa blood clot preventer are largely irreversible, according to the Journal of Neurosurgery
The recently approved drug is the first in a new class of oral medicines called direct thrombin inhibitors, approved to prevent strokes among patients with a dangerous irregular heartbeat called atrial fibrillation that mostly affects the elderly.
U.S. regulators said in December they were evaluating other cases of bleeding associated with the drug, whose chemical name is dabigatran, but advised patients to continue the medicine for now.
Three doctors from the University of Utah monitored and described the worsening condition, and ultimate death, of the 83-year-old man who was evaluated at their medical center for what seemed at first a rather routine fall, according to the report Tuesday in the journal's online edition.
Initially, the patient was fully alert and oriented and could respond to verbal commands, and his neurological exam produced no findings of great concern, the clinicians said.
They said CT scans revealed small, superficial areas of hemorrhage in his brain, but that within two hours after arriving at the hospital new scans showed extensive progression of brain hemorrhaging.
Efforts to stop the hemorrhaging, including intravenous fluids and a protein called recombinant factor VIIa, proved ineffective and the patient fell into a deep coma and died soon afterward, the report said.
"In the event of traumatic hemorrhage in patients receiving dabigatran … there are currently no effective reversal agents" to neutralize the drug, the report said.
Familiarity with Pradaxa is critical in order for medical personnel to take quick action with admittedly limited available means to control catastrophic bleeding, the report said.
Researchers speculated that dialysis might remove 35 percent to 60 percent of Pradaxa from the bloodstream in two to three hours, but noted that option was not taken with the elderly patient. "By the time of his deterioration it was too late to implement effectively."
Since balance problems and falls are common for elderly patients, cases of brain hemorrhage even from a minor trauma are likely to increase as more patients get prescribed Pradaxa, the researchers said.
"Bleeding is unfortunately one of the adverse effects of all anticoagulants," said John Smith, senior vice president for clinical development at Boehringer Ingelheim.
Although there is no antidote to Pradaxa that could control bleeding, including among fall victims like the elderly man, Smith said patients taking Pradaxa in a large clinical trial had a 59 percent lower overall incidence of intracranial bleeding than patients taking warfarin.
Pradaxa was approved by U.S. regulators in October 2010 for stroke prevention in patients with atrial fibrillation. It is the first of a new crop of blood clot preventers meant to replace warfarin — a longtime oral treatment that carries serious bleeding risks and requires routine blood monitoring and stringent dietary restrictions.
The report said patients taking the highest dose of Pradaxa in a large clinical trial sponsored by Boehringer had a similar overall rate of brain hemorrhage as those taking warfarin, while having a lower annual incidence of stroke. But the lack of a reversal agent in the event of catastrophic hemorrhage remains a handicap, they said.
The new medicine from privately held German drugmaker Boehringer Ingelheim competes with Xarelto, a pill from Johnson & Johnson and Bayer AG, approved four months ago in the United States that works by blocking a protein called Factor Xa.
Another Factor Xa inhibitor from Bristol-Myers Squibb Co and Pfizer Inc, called Eliquis, is being reviewed by the U.S. Food and Drug Administration for approval.
It is deemed by Wall Street to be the best of the new oral anticoagulants because it proved both safer and more effective than warfarin in large clinical trials. Industry analysts have speculated Eliquis could reap annual sales of $4 billion or more.