Drug makers Bayer AG and Johnson & Johnson’s new blood clot preventing drug can provide life-saving benefits at very low doses in patients who suffer from acute coronary syndrome finds a new clinical trial.
This was a large, late-stage clinical trial – the ATLAS study, the results of which were presented on Sunday at American Heart Association meeting in Orlando, Florida. It was noted that Xarelto or Rivaroxaban, reduced the risk of death by more than 30 percent in patients who have had an ACS episode, typically a heart attack caused by a blocked coronary artery. Xarelto was added on top of blood thinners that are now the standard of care.
This could change therapy in an estimated 1.2 million Americans treated for ACS each year and could open up a market worth up to $3 billion for the drug's manufacturers report Reuters. The companies plan to seek approval for the use by year's end.
“We have seen with this trial a new standard of anti-thrombotic therapy emerge,” said Dr. Paul Armstrong, professor of medicine at the University of Alberta, Edmonton, who provided commentary on the Xarelto trial at the American Heart Association scientific meeting in Orlando, where the study's details were unveiled. It is noteworthy that apixaban from Bristol-Myers Squibb and Pfizer, and Merck's vorapaxar each failed to meet the main goal of separate, unrelated studies presented at the meeting attended by thousands of doctors and researchers.
In the ATLAS study of 15,526 patients, those who received 2.5 milligrams of Xarelto twice a day on top of current standard therapy had the risk of cardiovascular death cut by 34 percent and all causes of death by 32 percent compared to patients on Plavix and aspirin, or just aspirin.
“Until now we have only used anti-platelet therapy and now we have another class of drug that appears to provide additive benefit, so I think that is a landmark event,” Dr. Raymond Gibbons of the Mayo Clinic said.
On the flip side the Xarelto patients did have a significantly higher incidence of major bleeding, including intracranial bleeding, but no increase in fatal bleeds. Researchers said the lower death rate overcame the bleeding risk. “You only have to treat 56 patients to save a life. It's hard not to be excited by the mortality benefit,” said Dr. Michael Gibson, the study's lead investigator, who presented the results at the meeting. “If it is approved (for this use) I think it will be widely adopted,” Gibson said. Major bleeding episodes occurred in 2.4 percent of patients on the high dose of Xarelto and 1.8 percent of those on the low dose, versus 0.6 percent of those on placebo.
“The mortality difference was pretty impressive,” said Deepak Bhatt, chief of cardiology at the VA Boston Healthcare System and director of the interventional cardiovascular program at Brigham and Women’s Hospital in Boston, in an interview. “It’s hard in cardiovascular medicine to find trials with a mortality benefit.”
“We are really excited about this result,” said Peter DiBattiste, global therapeutic area head of cardiovascular disease at Johnson & Johnson, in an interview. “This is a significant advance here over the standard of care.”
“Although we have made a lot of progress in caring for these patients in the hospital, once they leave they still have significant risks and high death rates,” said Eugene Braunwald, professor at Harvard Medical School and study author at Brigham and Women’s Hospital in Boston. “The statistical benefit for the very low dose is powerful.”
Still, the increased bleeding seen with Xarelto is something doctors and patients need to keep in mind when determining treatment, Braunwald said. “You have to take serious bleeding seriously,” he said. “I would rather have a patient have a serious bleed who walks out of the hospital than someone who dies without a bleed.” “The very low dose was better on efficacy by a lot because it showed a reduction in mortality, a smaller increase in bleeding and it wasn’t associated with fatal bleeding,” Braunwald said.
Xarelto inhibits a protein called Factor Xa involved in the blood clotting process. Earlier this month, Xarelto won U.S. approval on Nov. 17 for preventing strokes in patients with a dangerously irregular heartbeat called atrial fibrillation, considered to be by far the largest and most lucrative use for the new generation of blood thinners at an estimated $10 billion. Pradaxa is also approved in those patients.
The results are being published in the New England Journal of Medicine in conjunction with the conference.
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