Nov. 15, 2010 (Chicago) -- The experimental anticlotting pill Xarelto works at least as well as standard warfarin at preventing stroke and blood clots in people with irregular heart rhythms from atrial fibrillation, researchers report.
The rate of major brain bleeds, a key concern, was lower among patients on Xarelto, says Robert Califf, MD, of Duke University in Durham, N.C.
Overall, the rates of bleeding and adverse events were similar among people taking Xarelto and those taking placebo.
If approved by the FDA, Xarelto will offer an alternative to the old standby warfarin, which many people can't or won't take, doctors say.
Xarelto vs. Warfarin
In the study, 1.7% of people taking Xarelto had a stroke or a blood clot in another part of the body, compared with 2.2% of those given warfarin.
When the analysis was adjusted to include people who stopped taking the drug or switched to another treatment before the trial was complete, 2.1% of those on Xarelto and 2.4% of those on warfarin had a stroke or a clot, a difference so small it could be due to chance.
Both ways of looking at the data have their pros and cons, Califf says. But either way, "we have a drug you can take once daily, without monitoring, that is at least as good as warfarin and carries no additional risks," he says.
As for safety, 55 patients taking Xarelto experienced "the more worrisome" brain bleeds compared with 84 on warfarin, Califf says. This translates to a 33% lower risk of getting a major brain bleed if you take Xarelto, he says.
People treated with Xarelto also had fewer critical organ bleeds and were less likely to die from a bleed, compared with those treated with warfarin. But they were more likely to have drops in hemoglobin or bleeds requiring transfusions, both of which are also considered major bleeds.
Patients on Xarelto were also slightly more likely to have minor bleeds such as nosebleeds, Califf says.
Xarelto was associated with fewer deaths -- 582 vs. 632 in the warfarin group -- but the difference could have been due to chance.
There was no evidence the new drug caused liver problems, which also had been a worry, he says.
The study involved 7,111 patients on Xarelto and 7,125 patients on warfarin.
Califf presented the findings at a news briefing at the American Heart Association meeting.
"This was a very high-risk population," making the results even more impressive, Califf says. The average age was about 73, and 44% were 75 or older. More than half of them had already suffered a stroke or mini-stroke known as a transient ischemic attack.
Participants entered the study between December 2006 and May 2010 and were followed for an average of 19 months.
The new findings, combined with those from a recent study showing Xarelto was as safe and effective as warfarin at dissolving potentially deadly blood clots in the legs, is expected to lead to FDA approval of the drug, doctors say.
The study followed patients with atrial fibrillation (AF), a condition characterized by irregular heart rhythms. Many people with atrial fibrillation are more likely to suffer a stroke because their weakened heartbeats allow blood to pool in an upper chamber of the heart. Pooled blood is more likely to form clots, which can travel to the brain and cause a stroke.
Warfarin is the usual treatment to reduce the risk of stroke, but up to half of patients can't take it due to increased bleeding risk or drug interactions, or refuse to take it. If too much is given, you can suffer a dangerous bleed; too little, and you’re at risk for a deadly blood clot. You also have to be careful not to eat too many green leafy vegetables, which can interfere with its action.
Aspirin is sometimes used as a treatment in these patients, but it's less effective. So there's a race on to find a better alternative.
The first of the new anticlotting drugs, Pradaxa, was approved by the FDA last month for the prevention of stroke in patients with AF. In addition to Xarelto, other anticlotting drugs in development include apixaban, edoxaban, and betrixaban.
American Heart Association spokesman Raymond Gibbons, MD, of the Mayo Clinic in Rochester, Minn., tells WebMD that "it's very clear we need alternatives for the millions of Americans who need [anticlotting drugs] for AF."
That said, "Some of my patients do very well on the [much cheaper] warfarin," says Gibbons, who was not involved with the work.
While no price has been set for Xarelto in the U.S., Pradaxa is expected to cost more than $6 per day. Generic warfarin costs much less than $1 a day, although the price of regular blood tests and insurance co-pays needs to be weighed in, Gibbons says.
The drugs are part of a class called Factor Xa inhibitors. They interfere with our body's own clotting mechanism, which, when out of control, can lead to strokes in the setting of AF or clots in the leg that can travel to the lung.
Johnson & Johnson and Bayer HealthCare funded the new study.
This study was presented at a medical conference. The findings should be considered preliminary as they have not yet undergone the "peer review" process, in which outside experts scrutinize the data prior to publication in a medical journal.