Comparing the New Blood Thinners to Warfarin
By Kathleen Doheny
Reviewed by Michael W. Smith, MD
May 31, 2013 -- More than 2 million Americans have an abnormal heart rhythm known as atrial fibrillation, raising their risk of blood clots leading to stroke. For many years, the blood thinner Coumadin (warfarin) was the only game in town to help lower that stroke risk.
In the past 3 years, though, three new blood thinners, also called anticoagulants, have been FDA-approved for atrial fibrillation.
WebMD asked two doctors to compare them to warfarin and describe the risks and benefits of each. Neither doctor has ties to the drug companies making the blood thinners.
New Drugs in Town
All three new drugs are approved for atrial fibrillation treatment in people who do not have heart valve problems or artificial valves. One of the three also has FDA approval for additional conditions.
Atrial fibrillation disrupts the flow of blood through the heart. As blood pools, it's more likely to form clots that can travel to the brain, causing a stroke.
The new drugs are different in some respects but work in the same general way. ''All of them work on the clotting 'cascade,'" says John Doherty, MD. He is a professor of medicine at the Thomas Jefferson University School of Medicine, Philadelphia, and a member of the American College of Cardiology's Anticoagulation Initiative.
That cascade ''is a series of events by which different compounds are generated and ultimately result in blood coagulation [clotting]."
The three new drugs, which target various points along that cascade, include:
Pradaxa (dabigatran). It was approved by the FDA in October 2010 for prevention of stroke and blood clots in people with atrial fibrillation.
Xarelto (rivaroxaban). It was approved in November 2011, to treat atrial fibrillation. It had been approved earlier to lower the risk of blood clots after hip and knee replacements.
In November 2012, the FDA also approved it to treat deep vein thrombosis, (blood clots that occur usually in the lower leg and thigh) and pulmonary embolism (the condition that results when a blood clot from a vein breaks off and travels to an artery in the lungs and blocks blood flow.)
Eliquis (apixaban). It was approved in December 2012 to lower the risk of stroke and dangerous blood clots in patients with atrial fibrillation.
"We are excited there are these new options, but each patient will have to have a conversation with their physician and decide what is appropriate for them," says Clyde Yancy, MD. Yancy is chief of cardiology at Feinberg School of Medicine, Northwestern University, and past president of the American Heart Association.
While the new drugs offer some benefits over warfarin, some patients may do better to stay on the old drug if they are doing well, says Doherty.
Yancy agrees. "If you are doing well on warfarin, there is no reason to take a more expensive drug unless the other advantages are so uniquely important it's worth the transition," he says.
Warfarin was approved by the FDA in 1954. Experts say it's a difficult drug to take, because the optimal dose varies from person to person. Dosage can depend on diet, age, and other medications being taken.
The dosing is delicate. Give too much, and the risk of bleeding rises, sometimes dangerously. Give too little and the stroke risk remains.
Patients must get blood tests monthly or more often and watch their intake of vitamin K, found in foods such as spinach, kale, and chard. Too much vitamin K in the blood can lessen the effectiveness of warfarin.
"Patients have to keep the level [of these vitamin-K rich foods] constant, and at a fairly moderate level," Doherty says.
Overview of the New Drugs
The three new drugs share some benefits and downsides, Yancy and Doherty say.
"With any of the three, there is no longer a requirement for constant surveillance," Yancy says. "The dietary issues go away as well."
While individual trials of the three new drugs have found different reductions in stroke risk, "in large measure we think of these [new] drugs as similar," Yancy says. Besides lowering stroke risk, "all three drugs are associated with a lesser likelihood of bleeding that could be troublesome." He's referring to intracranial hemorrhage, or bleeding into the brain, a known side effect of warfarin.
However, if blood levels rise too much with the new drugs, there is no ''antidote'' as there is with warfarin. If blood levels of warfarin rise too much, giving vitamin K brings them down, Yancy says.
With the new drugs, he says, ''there's no antidote for overshooting, unless it's fresh plasma, which has its own risks." With time, the drugs clear the body.
High blood levels of the new drugs can become an issue if a patient needs emergency surgery, Doherty says, as that would raise bleeding risk.
Comparing Pradaxa, Xarelto, Eliquis
No head-to-head comparison of the three new drugs has been made. However, researchers looked at data from clinical trials for all three new drugs and conducted an indirect comparison.
That method has limitations, though, because the patients studied vary from trial to trial and different doses were studied.
Even so, in this comparison, published in 2012 in the Journal of the American College of Cardiology, the researchers overall found ''no profound significant differences" in effectiveness among the three.
Smaller differences, such as the dosing schedules, may persuade a doctor to choose one over the other, Yancy says.
Here's a closer look at the three new blood thinners.
The usual dose of Pradaxa is a 150-milligram tablet, taken twice a day, with or without food.
In studies comparing it to warfarin, those on the newer drug had fewer strokes, according to the FDA.
However, after Pradaxa was approved, the FDA received a large number of reports of bleeding, such as gastrointestinal and brain bleeds.
The FDA investigated, concluding in 2012 that the bleeding risks do not appear any higher than in people taking warfarin.
For stroke risk reduction, the usual dose of Xarelto is 20 milligrams once a day, taken with the evening meal. Doses can be different for other conditions.
The once-daily dose may appeal to some patients, Doherty says. It's easier to remember than multiple pills.
In a clinical trial with more than 14,000 patients, Xarelto was found similar to warfarin in the ability to prevent stroke, according to the FDA.
In studies on hip and knee replacement patients, those taking Xarelto were much less likely than those on other anti-clot therapies to have clot problems, according to the FDA.
In studies on preventing deep vein thrombosis and pulmonary embolism, Xarelto was as effective as another treatment combining Lovenox (enoxaparin) and warfarin.
The usual dose of Eliquis is 5 milligrams, taken twice a day with or without food.
In a study of more than 18,000 patients comparing Eliquis with warfarin, those on Eliquis were 21% less likely to have a stroke, according to the FDA.
SOURCES: Clyde W. Yancy, MD, Magerstadt Professor of Medicine and chief of cardiology, Northwestern University Feinberg School of Medicine; associated director of the Bluhm Cardiovascular Institute, Northwestern Memorial Hospital, Chicago; past president, American Heart Association. John U. Doherty, MD, professor of medicine, Thomas Jefferson School of Medicine, Philadelphia; member, American College of Cardiology Anticoagulation Initiative (for the safe and appropriate use of new medicines). FDA. Lip, G. Journal of the American College of Cardiology, August, 2012. Mary Lewis, Boehringer-Ingelheim spokesperson. Kristina Chang, spokesperson, Janssen Global Services. Christina Trank, spokesperson, Bristol-Myers Squibb.
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