A new anti-blood clotting drug – Xarelto (rivaroxaban) has shown clinical success. It may help people with “acute coronary syndrome” lower their risk of death, subsequent heart attack or stroke, a new study finds. Acute coronary syndrome is term that includes people with angina or prior history of heart attack.
The finding “opens up a new area for treating this very common condition,” said study co-author Dr. Eugene Braunwald, professor of medicine at Harvard Medical School and a cardiologist at Brigham and Women’s Hospital in Boston.
Xarelto is currently approved by the U.S Food and Drug Administration to treat an abnormal heart rhythm called atrial fibrillation and to prevent the formation of blood clots after hip and knee replacement surgery.
The new study, funded by the drug’s makers, Johnson & Johnson and Bayer Healthcare, is being published Nov. 13 in the New England Journal of Medicine to coincide with its presentation at the annual meeting of the American Heart Association in Orlando, Fla.
The new trial included 15,526 people who had been hospitalized for acute coronary syndrome. Participants received either a low dose (5 milligrams) or a very low dose (2.5 mg) of the new blood thinner or a placebo, in addition to standard care. The medications were given twice daily for an average of 13 months.
Results showed that people who received either dosage of Xarelto had a lower risk of heart attack, stroke or death when compared to their counterparts given a placebo. Specifically, there was a 16 percent decrease among patients in the 2.5-mg group and a 15 percent decrease in the 5-mg group, the researchers reported. Among the participants taking the 2.5-mg dose, there was a 34 percent reduced risk of cardiovascular death and a 32 percent lower risk for death from any cause. Similar reductions were not seen among people taking the 5-mg dose, however.
However, addition of the new drug did boost the odds of a common blood-thinner side effect: bleeding, including bleeds within the brain. However, this increase in risk was confined to not fatal bleeding the research team reported, and the incidence of bleeding fell when patients took the smaller versus the larger dose of Xarelto.
Braunwald said risks for bleeding must always be balanced against the benefits of any anti-clotting medication. “I’d rather have a patient walk out of a hospital with a bleed than [leave through] the morgue,” he said.
Another study author, Dr. C. Michael Gibson, added, “We have not seen a mortality reduction like this in cardiology for a few decades,” said Gibson, who is chief of clinical research in the Division of Cardiology at Beth Israel Deaconess Medical Center in Boston. “This is secondary prevention for people who have weathered the storm and survived.”
The benefit from Xarelto was consistent across all subgroups, Gibson said. “There is more bleeding,” he said, “but no excess fatal bleeding or bleeding that leads to disability. I think it will be a game-changer.”
Before moving forward, Xarelto needs further study among people who are at high risk for bleeding, Drs. Matthew T. Roe and E. Magnus Ohman of Duke University Medical Center in Durham, N.C., wrote in an accompanying editorial in the journal. They point out that better ways of predicting which patients are at risk for drug-related bleeds is also needed. Still, they wrote, “the results of this study indicate that rivaroxaban [Xarelto] will play an important role in the future of optimized secondary prevention.”
For his part, American Heart Association President Dr. Gordon F. Tomaselli said that Xarelto and other, newer drugs may offer options to patients beyond warfarin. Other members of this relatively new class of drugs now include Pradaxa (dabigatran) and Brilinta (ticagrelor). “Xarelto and the others are important new medications that are easier for patients to take and do not interact as much with other medications or foods,” said Tomaselli, who is chief of cardiology at Johns Hopkins University School of Medicine in Baltimore. “They do cost more, but they don’t require the monitoring infrastructure including frequent blood draws,” he explained. “For many people who hate taking warfarin, because it interferes with what they eat or take, these drugs are good alternatives,” he said.
“The mortality difference was pretty impressive,” said Deepak Bhatt, 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.”
Other anti-clotting medications in development did not perform as well, according to two other studies also presented Sunday at the meeting, and also published in the New England Journal of Medicine.
In another trial, the drug apixaban (Eliquis) was pitted against another mainstay blood thinner, enoxaparin (Lovenox), in more than 6,500 patients with congestive heart failure at high risk for dangerous clots. Researchers led by Dr. Samuel Goldhaber of Brigham and Women’s Hospital and Harvard Medical School found that Eliquis did not outperform Lovenox and was also linked to more bleeding.
One study, led by Dr. Pierlugi Tricoci of Duke University, looked at a blood thinner called vorapaxar. In a study involving nearly 13,000 patients with acute coronary syndromes, adding vorapaxar to standard treatment did not significantly reduce patients’ risk of dying from heart disease, risk of heart attack, stroke or re-hospitalization. The drug did boost patients’ odds for major bleeding, however.
The vorapaxar study was funded by drug maker Merck, while Bristol-Myers Squibb and Pfizer supported the Eliquis/Lovenox trial. “This is going to be such a competitive field as multiple drugs jockey for position,” said Robert Harrington, director of Duke University’s Clinical Research Institute in Durham, North Carolina. “There is going to be some time before people figure out” how to use the new treatments, he said.
About 1.2 million people in the United States alone are discharged from hospitals each year after a heart attack or heart-related unstable chest pain. Currently, the only anti-coagulant prescribed for such patients when they leave the hospital is warfarin. But difficulties in managing the 50-year-old medicine means it is not often used to prevent heart attacks. Numerous other trials have attempted to find a better alternative, but have failed.
The Xarelto study was funded by New Brunswick, New Jersey- based Johnson & Johnson, which owns U.S. rights, and Leverkusen, Germany-based Bayer, which sells the treatment in Europe.
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