Sept. 1, 2010 (Stockholm, Sweden) -- Two experimental anticlotting drugs showed impressive results at preventing deadly blood clots, doctors say.
If approved, they will offer alternatives to the old standby, warfarin, which many people can't or won't take.
In one study of 5,600 patients who couldn't or wouldn't use warfarin, apixaban beat aspirin at preventing dangerous clots or strokes.
In the other study of more than 3,400 patients, the new pill Xarelto was as safe and effective as warfarin at dissolving potentially deadly blood clots in the legs and preventing new ones.
Both studies were presented at the European Society of Cardiology Congress.
Apixaban cut the risk of stroke by more than half compared with aspirin, says researcher Stuart Connolly, MD, of McMaster University in Hamilton, Ontario, Canada.
The rate of major bleeding, the key concern, was no higher among patients on apixaban, he says.
The late-stage phase III study was stopped early after apixaban's advantages became clear, Connolly tells WebMD.
Drawbacks of Warfarin
The study followed patients with atrial fibrillation (AF), a condition characterized by irregular heart rhythms. They're five times more likely to suffer a stroke than people without AF because their erratic 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 block blood flow, causing a stroke.
Warfarin is the usual treatment, but up to half of patients can't take it because of increased bleeding risk or drug interactions, or refuse to take it. If too much is given, you can suffer a dangerous bleed; take too little, and you're at risk for a deadly blood clot related to the AF.
Aspirin is the usual care in patients who cannot take warfarin, but it's less effective. So there's a race on to find a better alternative, with apixaban, Xarelto, and a third drug, Pradaxa, leading the pack. Other anticlotting drugs in development include edoxaban and betrixaban.
In the new study, apixaban reduced the rate of strokes or major clots by 54%. The annual rate of strokes in patients on apixaban was 1.6% vs. 3.6% for those on aspirin, Connolly says.
The annual rate of major bleeding, including bleeds to the brain, was 1.2% for aspirin and 1.4% for apixaban, a difference so small it could have been due to chance.
The apixaban results were "truly impressive," Connolly says.
Apixaban is set to be reviewed by FDA advisers later this month.
Findings of another study, in which apixaban is being pitted against warfarin, are due out next year.
The study was funded by Bristol-Myers Squibb and Pfizer, from which Connolly received research grants and consulting fees.
Xarelto Prevents Deadly Leg Clots
The Xarelto study looked at preventing deadly blood clots in the legs, a condition known as deep vein thrombosis, or DVT.
The study was designed to show that it worked at least as well as standard treatment, and that goal was met.
The standard treatment of injecting Lovenox followed by warfarin pills is "quite effective, but cumbersome to use," says researcher Harry R. Buller, MD, of the Academic Medical Center in Amsterdam.
In the late-stage phase III study, 2.1% of patients on Xarelto suffered recurrent clots, compared with 3% on standard treatment.
While the difference was so small it could have been due to chance, "Xarelto came close to demonstrating superiority," Buller tells WebMD.
The rate of major bleeds, the primary safety concern, was the same in both groups: 8.1%. And there was no evidence the new drug caused liver problems, which also had been a worry, Buller says.
"This simple single drug approach provides patients with an attractive alternative for the prevention and treatment of deep vein thrombosis," he says.
The Xarelto trial was funded by its maker, Bayer Schering Pharma.
New Anticlotting Drugs: Experts Comment
Upon hearing the data, American College of Cardiology President Ralph Brindis, MD, of Kaiser Permanente in San Francisco, says, "Patients and physicians alike have been looking for a [warfarin alternative] that doesn't require testing, is simple to use, and is safe and effective for the treatment of DVT and for the prevention of stroke in AF."
"These drugs appear to meet that need," he tells WebMD.
Harald Darius, MD, ofVivantes Neukoelln Medical Center in Berlin, who was asked to put the findings into perspective for attendees, notes that questions remain.
"I'm positive we are facing a new era of antithrombotic therapy in patients with DVT, but with some questions to be resolved. For example, what is the optimal duration of treatment? Is it three months, six months, 12 months, or even 24 months?" he says.
New Anticlotting Drugs: How They Work
The new drugs are part of a class called factor Xa inhibitors. They interfere with the body's clotting mechanism.
When we get a cut, the body calls on a blood clotting pathway to stop the bleed, Brindis explains. "But if it gets out of control, problems develop: clots in the leg that can travel to the lung, or strokes in the setting of AF.
"Interfering with this normal clotting mechanism will minimize the risk of these problems. The downside is an increase in the risk of unwanted bleeds, so it was reassuring that was not observed," Brindis tells WebMD.
No price has been set for either drug in the U.S, according to company spokespeople. Both companies hope their drugs will eventually be approved for both uses: strokes in AF patients and DVT.
These studies were 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.