Three new game-changing anticoagulants have been developed for the prevention of strokes in people with atrial fibrillation. The new designer drugs dabigatran, rivaroxaban and apixaban offer significant benefits compared to decades-old warfarin, but there are some downsides to consider.
More than 2.7 million Americans have atrial fibrillation today and an estimated 12 million may have it by 2050. Atrial fibrillation is an irregular heartbeat that fails to pump blood properly, leading to the risk of blood-clot formation that can cause a stroke, especially in those who have other risk factors like high blood pressure or heart disease. In fact, atrial fibrillation is estimated to be a major culprit in 15 to 20 percent of ischemic strokes, those caused when a clot blocks blood flow to the brain.
Many people with this disorder do not realize they have a problem with their heart because symptoms like heart palpitations, dizziness or chest pains can come and go or be unnoticeable. Atrial fibrillation is very uncommon in young people and risk increases with age: the median age for men is 67 years and for women, 75 years.
The anticoagulant warfarin works fairly well, preventing almost two-thirds of strokes in people who have atrial fibrillation. Warfarin thins blood by interfering with vitamin K, which is necessary for normal blood clotting. But warfarin comes with a significantly increased risk of bleeding that requires careful monthly blood monitoring. Also, patients must juggle a long list of foods and drugs that can cause dangerous interactions. Due to this challenging profile, about 50% of patients who should be taking warfarin are not doing so, putting their health at significant risk.
The new blockbuster drugs require no monthly blood monitoring and there is no long list of foods to avoid. Different from warfarin, they act directly on more specific blood clotting factors: thrombin or factor Xa. “These new drugs are more consistent in their biologic effect. They all have fewer food and drug interactions, allow more consistent absorption and anticoagulant effects, and they don’t require monitoring,” says John H.P. Alexander, MD, MHS, cardiologist at Duke University Medical Center and co-author of the ARISTOTLE study on apixaban versus warfarin.
How did the new anticoagulants compare to warfarin in large-scale clinical trials?
Dabigatran (Pradaxa) In the RE-LY study, dabigatran (150 mg) was found to reduce the risk of stroke and systemic embolism (a major blood clot blockage) by 35% versus warfarin but with similar rates of major bleeding. Dabigatran users had a greater risk of gastrointestinal bleeding and an increased risk of heart attack compared to the warfarin group. The FDA approved the drug in October 2010 and is now conducting a safety review to follow up on post-market reports of serious bleeding events.
Rivaroxaban (Xarelto) Rivaroxaban performed the same as warfarin for reducing the risk of stroke and systemic embolism in the ROCKET AF study. The risk of major bleeding in general was the same for both medications, but intracranial and fatal bleeding occurred less often in the rivaroxaban group. Major bleeding from a gastrointestinal site was more common for rivaroxaban but the incidence was small at about 3%. The FDA approved Rivaroxaban in July 2011.
Apixaban (ELIQUIS) The newest star of the group is apixaban, currently before the FDA for priority review in the US and already approved for sale in the EU to prevent blood clotting after orthopedic surgery. In the ARISTOTLE study, apixaban significantly reduced the risk of stroke or systemic embolism by 21%, major bleeding by 31% and death by 11% compared to the use of warfarin. The anticipated date for FDA approval for apixaban is June 28, 2012.
So, should people taking warfarin switch to a new designer drug? Not necessarily. The two currently available cost significantly more than warfarin. Dr. Alexander says, “The cost element is not trivial. There are many millions of patients with atrial fibrillation and it’s true that for many of them we will improve their outcomes by using these new drugs versus warfarin, but that will be at a substantial cost to our healthcare system. We need to consider those patients who do fine on warfarin and don’t need to switch.”
CONNECT THE DOTS
Visit the Coumadin website to read important safety information and review the full US prescribing information about warfarin. Visit the Pradaxa website to learn more about dabigatran and the Xarelto website to learn more about rivaroxaban. You can also find Medication Guides at the FDA’s site.
Originally published on GE Healthy Outlook, March 26, 2012. Copyright Jane Langille.
