Researchers find that an experimental anticlotting pill Eliquis is more effective than standard drug, warfarin, at preventing strokes in people with a heart condition that puts them at high risk of blood clots and stroke. The new drug also known as apixaban, cut the risk of stroke by 21% compared with warfarin in people with atrial fibrillation (AF). It lowered the risk of dying by 11%.
The side effect of serious internal bleeding, the key safety concern of anticlotting medication, was reduced by 31% with Eliquis compared to warfarin. Two other anticlotting pills studied as 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, 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 Atrial fibrillation 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 The New England Journal of Medicine.
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, one can suffer a side effect of a dangerous bleed. In too little doses, and the risk of a potentially deadly blood clot increases further.
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, 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 said.
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.
“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.
Some cardiologists said it's too early to declare a winner among the new agents. “Aristotle is a great result and there's going to be a lot of enthusiasm,” said Jessica Mega, a cardiologist at Brigham and Women's Hospital in Boston. While the absolute reduction in serious events was small—for every 1,000 patients treated for 1.8 years, apixaban prevented six strokes, 15 cases of major bleeding and eight deaths compared with warfarin—such events are devastating, she said. But she said that making comparisons between drugs based on studies in which they weren't tested head to head isn't reliable. “The nuances between them will be teased out” in further study and as they are used by clinicians, she said.
In an editorial accompanying publication of the study in the New England Journal of Medicine, Dr. Mega cited all three drugs, plus at least one more in development, as representing a “new era” in anticoagulation. “This is good news for patients and for the drugs overall,” Dr. Mega said. “It's a real advance.”
Dr. Granger, said cost is likely to be the “biggest single barrier” to use of any of the new agents. He said he hopes competition from approval of additional agents will lead leads to lower costs.
Commenting on the latest study, Dr. Gregg C. Fonarow, a professor of cardiology at the University of California, Los Angeles agreed that “atrial fibrillation substantially increases the risk of stroke and death.” Warfarin reduces the risk of stroke in patients with atrial fibrillation, but it also boosts the odds of bleeding and is often difficult to manage, he said. “Apixaban is now the first oral anticoagulant [blood thinner] to show a statistically significant improvement in survival over warfarin in atrial fibrillation patients,” Fonarow said. “This represents a very important therapeutic advance in the care of patients with atrial fibrillation.”
Exploring the current use and future of alternatives to traditional informed consent in acute stroke trials