Aug. 29, 2011 (Paris) -- The experimental anticlotting pill Eliquis beat out the standard drug, warfarin, at preventing strokes in people with a heart condition that puts them at high risk of blood clots and stroke, researchers report.
Two other anticlotting pills in the race to find warfarin alternatives, Pradaxa and Xarelto, have also shown benefits over the older treatment in major studies. But Eliquis is the first to reduce all three measures of stroke, deaths, and bleeds.
"This is a real home run ... another dagger in the heart of warfarin for stroke prevention," says Ralph Brindis, MD, a cardiologist at Kaiser Permanente in Oakland, Calif. Brindis is immediate past president of the American College of Cardiology. He was not involved with the work.
Results of the two-year study pitting Eliquis against warfarin in 18,201 people with AF and at least one other risk factor for stroke were presented here at the European Society of Cardiology Congress 2011. The study was also published online in TheNew England Journal of Medicine.
Atrial Fibrillation and Stroke Risk
Atrial fibrillation, a condition characterized by irregular heart rhythms, affects 2.6 million Americans, with risk increasing with age. People with AF are more likely to suffer a stroke than people without AF because their erratic heartbeats allow blood to pool and form clots in an upper chamber of the heart. The clots can travel to the brain and block blood flow, causing a stroke.
Warfarin, which is also sold under the brand names Coumadin and Jantoven, has been the standard treatment for AF for decades. It can cut stroke risk by up to 70%. But frequent blood tests are needed to make sure the patient is getting a correct dose. If too much is given, you can suffer a side effect of a dangerous bleed. Take too little, and the risk of a potentially deadly blood clot increases further.
Because it works by blocking vitamin K, eating foods that are high in the nutrient, like dark leafy greens, can make warfarin less effective. Many drugs, including some antibiotics and painkillers, can interact with the drug, blocking or enhancing its effect.
As a result, only about half of patients who can benefit from the drug actually take it.
Overall, 1.3% of patients per year in the Eliquis group suffered a stroke or major blood clot vs. 1.6% per year in the warfarin group. The rate of serious internal bleeding was 2.1% per year in the Eliquis group vs. 3.1% per year in the warfarin group. And 3.5% of patients per year in the Eliquis group died vs. 3.9% per year in the warfarin group.
This means that for every 1,000 patients treated for nearly two years, Eliquis, as compared with warfarin, prevented six strokes, 15 serious bleeding episodes, and eight deaths, says study head Christopher B. Granger, MD, of Duke University Medical Center in Durham, N.C.
The benefit in stroke prevention was driven mainly by the difference in bleeding (hemorrhagic) stroke, with Eliquis preventing four hemorrhagic strokes per 1,000 patients and two clot-related (ischemic) strokes per 1,000 patients.
Eliquis bested warfarin in all subgroups of patients studied, regardless of age, gender, weight, or prior use of warfarin, among other characteristics, Granger tells WebMD.
Pros and Cons of New Drugs
The new drugs -- Eliquis, Pradaxa and Xarelto -- are all wins for patients, says Michael Bonn, MD. Bonn is chairman of the committee that chooses which studies to highlight at the meeting. He is also a cardiologist at University Hospital of Saarland in Homburg, Germany.
Bonn says the new drugs provide the same or better protection as warfarin, but without the need for frequent blood monitoring or food interactions.
There aren't any studies directly comparing the newer drugs to each other. But Eliquis appears to have some advantages over Pradaxa, which is already FDA approved for stroke prevention in AF patients, and Xarelto, which is approved for prevention of potentially deadly blood clots in the legs of patients undergoing joint replacement surgery, he tells WebMD. An FDA advisory committee is meeting next month to consider Xarelto for stroke prevention in AF.
For example, Xarelto worked at least as well as warfarin at preventing strokes. But unlike Eliquis, it did not improve survival. And the major study upon which approval of Pradaxa was based showed that drug was associated with higher rates of heart attack and stomach bleeds than warfarin.
But Pradaxa is the only drug to lower the rate of ischemic stroke, the type of stroke caused by blood clots, compared with warfarin. And while the other drugs have to be taken twice daily, Xarelto only has to be taken once a day, increasing the chance patients will take their medication as prescribed, Brindis says.
Another new anticlotting drug, edoxaban, is being tested in a different study, called the ENGAGE study.
Brindis notes that all the newer agents have some potential downsides.
For starters, warfarin is available generically for $4 a month, while Pradaxa can cost $160 a month.
And while doctors can give vitamin K to quickly reverse the effects of warfarin in the case of dangerous bleeding, there's no quick antidote for bleeding caused by the newer agents, he says.
"That's not a trivial issue. The rate of major bleeds in patients on anticlotting drugs is 2% to 3% per year," Brindis says.
Brindis and Bohm agree that the newer agents will probably prove most useful for patients being prescribed anticlotting drugs for the first time and those for whom warfarin dosing proves problematic.
"If warfarin has been working with no problems, and the patient isn't all upset about the blood work, there is no reason to switch," Brindis explains.
The Eliquis study, dubbed Aristotle, was funded by Bristol-Myers Squibb and Pfizer. Bristol-Myers said an application for approving Eliquis for AF will be filed with the FDA later this year.