Up to 1 in 5 strokes are the result of atrial fibrillation (AF), a condition that causes an abnormal heart rhythm. For more than 60 years, patients diagnosed with atrial fibrillation have been prescribed warfarin, a blood thinner that can significantly lower the risk of stroke. But warfarin, marketed under the brand names Coumadin and Jantoven, is associated with an elevated risk of bleeding in and around the brain.
Today, there are more anticoagulant options for lowering the risk of stroke, and they are increasingly being used as alternatives to warfarin. Since 2010, the Food and Drug Administration (FDA) has approved four additional oral anticoagulant drugs that are considered at least as effective as warfarin and pose what the FDA considers an acceptable risk of bleeding. In particular, the newer drugs are less likely than warfarin to cause bleeding in the brain that leads to stroke.
Nonetheless, all anticoagulants increase bleeding risk. When the newer drugs were first approved, medical experts were especially concerned that no antidote existed to reverse their blood-thinning effects.
However, a milestone was reached in the evolution of anticlotting drugs in 2015 when the FDA approved a reversal agent to counteract the effects of dabigatran (Pradaxa).
The antidote, idarucizumab (Praxbind), can stem uncontrolled bleeding—such as the kind that could result from Pradaxa’s anticoagulant effects—in a potentially life-threatening emergency situation. Thus, it provides a layer of protection for patients.
For the other newer anticoagulants—Xarelto (rivaroxaban), Eliquis (apixaban), and Savaysa (edoxaban)—doctors have turned to off-label use of a coagulation factor product, prothrombin complex concentrate, for reversal of bleeding.
Here are some points to consider when discussing treatment options with your doctor. It’s important to remember that most of the bleeding that occurs with anticoagulants is not serious, and does not cause the kind of permanent disability or death that strokes cause.
Warfarin, approved by the FDA in 1954, has been widely used to inhibit clot formation or prevent recurring episodes in people who have already developed a clot. Warfarin works by blocking an enzyme needed by the liver to produce substances that form blood clots (clotting factors).
For people with atrial fibrillation, warfarin has been shown to reduce the risk of stroke by two-thirds. Yet warfarin may also double the risk of intracranial hemorrhage—an accumulation of blood in the skull.
Warfarin is a difficult drug to manage, requiring patients to have frequent blood tests to determine if the prescribed dosage is sufficient to prevent blood clots, yet isn’t increasing the risk of excessive bleeding.
Several types of reversal agents, however, have been developed to counteract the effects of warfarin. If uncontrolled bleeding does occur due to a serious injury, these antidotes, including vitamin K and the drug Kcentra (prothrombin complex concentrate, human), can restore coagulation in people taking warfarin.
Pradaxa, the first of the four most recent blood thinners to have been approved by the FDA, works by blocking an enzyme called thrombin, which is involved in the formation of blood clots.
An ongoing review by the FDA, based on information from more than 134,000 Medicare patients from 2010 to 2012, found that Pradaxa was associated with a lower risk of clot-related strokes, bleeding in the brain, and death, when compared with warfarin.
Pradaxa was associated with an incidence rate (the likelihood of occurrence in a certain population) of 11.3 clot-related strokes, compared to 13.9 for warfarin. Pradaxa had a rate of 3.3 incidents of intracranial bleeding, compared with 9.6 for warfarin.
The FDA review also found that Pradaxa was associated with an increased risk of major gastrointestinal bleeding, when compared with warfarin—a risk that has been shown to increase with age. The incidence rate of GI bleeding in patients taking Pradaxa was 34.2, versus 26.5 for warfarin. Both drugs had a similar risk of causing heart attacks.
Despite these findings, the FDA still considers Pradaxa to have “a favorable benefit-to-risk profile.” The FDA has not instructed the drug manufacturer to make any changes to the current label or recommendations for use.
Reducing stroke risk
The other newer anticoagulants work by inhibiting a clotting protein called factor Xa. After evaluating clinical trials involving more than 50,000 people from around the world, the FDA concluded that all four newer drugs either had the same impact or were more effective in preventing stroke compared with warfarin, and did not cause an unacceptable risk of bleeding.
The FDA reported that the drugs had a substantially lower risk than warfarin of causing the type of bleeding that leads to a hemorrhagic stroke. The newer anticoagulants offer other benefits, including fewer interactions with food and other drugs, faster onset, and the lack of need for periodic blood monitoring.
Although fatal bleeding is rare in patients taking blood thinners, studies have shown that the death rate from bleeding caused by taking any of the newer anticoagulants is lower than it is from warfarin.
While Xarelto, Eliquis, and Savaysa do not have FDA-approved reversal agents available to counteract their effects, large clinical trials have determined that for all the anticoagulants used in atrial fibrillation, the benefit of preventing strokes outweighs the increased risk of bleeding.
FDA monitoring of the new medications continues as reversal agents make their way through the development pipeline. At least two drugs that may reverse the effects of these anticoagulants have been undergoing clinical trials.
Only about half of the 3 million people in the United States who have atrial fibrillation use anticoagulants. Patients with atrial fibrillation who are candidates for anticoagulants and do not use them are not being protected from the high risk of having a devastating stroke.
After a regimen of anticoagulants is started, many patients end up taking them for less than six months, instead of on a long-term basis as recommended. With the newer anticlotting drugs, however, eligible patients now have more treatment options.
Find out more about how you can prevent a stroke.