Boehringers Pradaxa Is Safe, Effective Alternative to Warfarin
Pradaxa prevented more strokes and damaging clots than warfarin without increasing the risk of major bleeding when given at a high dose, according to the results of a trial known as RE-LY. A lower dose of the experimental drug was as effective as warfarin with less bleeding in the study presented today at the European Society of Cardiology meeting in Barcelona.
Almost 4 percent of people aged 60 and older have atrial fibrillation, including about 7 million in the U.S. and Europe, and the number is increasing, doctors said. Treatment is with warfarin, which interacts with a long list of food and drugs and requires frequent blood tests to ensure patients take the right dose. Pradaxa would be given as a pill twice daily based on weight and doesnt require laboratory monitoring, researchers said.
“Were in an epidemic of atrial fibrillation, and its very difficult for patients to monitor their warfarin levels,” Alfred Bove, chief of cardiology at Temple University in Philadelphia and president of the American College of Cardiology, said in an interview. “This drug takes some of that away and is a major breakthrough for patients with atrial fibrillation.”
The research, simultaneously published in the New England Journal of Medicine, is the largest trial ever conducted in patients with atrial fibrillation and was originally designed show Pradaxa was equal to warfarin. The superior results may affect the way millions of them are treated, researchers said.
Game-Changer
The study of 18,113 patients found 1.11 percent of those on the high dose of Pradaxa had a stroke or clot known as an embolism within two years, compared with 1.53 percent of low dose patients and 1.69 percent of warfarin patients. Major bleeding occurred in 3.11 percent of high dose patients, 2.71 percent of low dose patients and 3.36 percent of warfarin users.
Strokes caused by bleeding in the brain were significantly less common in patients getting either dose of Pradaxa.
“In my view, this is an absolute game-changer,” said researcher Michael Ezekowitz, vice president of the Lankenau Institute for Medical Research and the Heart Center in Wynnewood, Pennsylvania. “I was amazed by the results,” he said in an interview.
Boehringer plans to file for regulatory approval of the drug as rapidly as possible, and expects to be able to sell the drug by the end of next year, Chief Executive Officer Andreas Barner said in a telephone interview.
Real Breakthrough
“Overall, this trial looks like the rare event of a real breakthrough,” he said. “For stroke prevention, I do believe there will be a clear move toward Pradaxa because the efficacy and safety results are so compelling. I am convinced that Pradaxa is the new gold standard.”
Merck & Co. also is working on a rival to Pradaxa known as betrixaban that it licensed from Portola Pharmaceuticals Inc. in July. The drug is in the second of three stages of testing.
Potential Questions
One big issue with the use of Pradaxa will be its price, said Clyde Yancy, medical director at Baylor Heart and Vascular Institute in Dallas, Texas, and president of the American Heart Association. While warfarin is available as an inexpensive generic medication, the cost of testing and dose adjustment can cost anywhere from $50 to $500 a month, he said.
There are other potential questions with Pradaxa, Yancy said in an interview. Heart attacks, though rare, occurred more often in patients getting Pradaxa in the study, as did abdominal pain and nausea, the study showed.
“Weve learned in cardiovascular medicine not to ignore these signs,” even when they arent large or fully understood, he said. “I would anticipate the Food and Drug Administration would come forward with a somewhat restrictive labeling,” targeting the drug for the higher risk patients while doctors get more comfortable with using the medicine, he said.
Still, only about half of patients with atrial fibrillation consistently stick with the medication, he said. The positive results seen in RE-LY have generated some sense of relief and enthusiasm, he said.
“Patients have wanted something easier to take for atrial fibrillation, and this may be it,” he said. “Sparing patients the agony of weekly tests – thats worth it.”