Afib News & Events
Researcher Reviews Clinical Trials of Rivaroxaban (Xarelto) and Dabigatran (Pradaxa) as Alternatives to Warfarin for Preventing Atrial Fibrillation Strokes
Dr. Elaine Hylek Reviews New Novel Anticoagulants for Atrial Fibrillation Stroke Prevention — Video
July 7, 2011
- Summary: An FDA Advisory Committee will review rivaroxaban (Xarelto) as an alternative to warfarin for stroke prevention in atrial fibrillation on September 8, 2011. In this video interview, Dr. Elaine Hylek discusses the results of clinical trials of rivaroxaban and the currently-approved dabigatran (Pradaxa).
- Reading and watching time: Approximately 10–12 minutes
In this video interview, Dr. Elaine Hylek, of Boston University, discusses new anticoagulant drugs for stroke prevention in atrial fibrillation.
For many years, warfarin (Coumadin) has been the only anticoagulant option for patients. Taking warfarin requires constant monitoring, and it can be a challenge for many patients. In addition to drug-drug interactions and food-drug interactions, warfarin can be affected by illness or heart failure. Dr. Hylek discusses the clinical trials results for two of the new anticoagulants that are alternatives to warfarin.
The RE-LY clinical trial of dabigatran, called Pradaxa in the marketplace, demonstrated dramatic results. Dabigatran is the first direct thrombin inhibitor, a new type of drug. The FDA approved dabigatran in October of 2010.
RE-LY investigators studied two doses, 150 milligrams and 110 milligrams, each taken twice a day. "The 150 milligram dose twice a day was shown to be more efficacious than warfarin for preventing stroke, which is a huge finding,” says Dr. Hylek. Additionally, the chances for intracranial hemorrhage (bleeding in the brain) decreased on both doses of dabigatran when compared to warfarin. While the 150 milligram dose was found to be more effective at stroke prevention and lowered the risk of intracranial hemorrhage, it was also found to have a larger risk of gastrointestinal bleeding than warfarin.
The Rocket AF trial demonstrated that rivaroxaban, which will be marketed as Xarelto, was as effective as warfarin (called "non-inferior" in clinical trials). This drug, called a Factor Xa (pronounced 10a) inhibitor, is slightly different from both dabigatran and warfarin in that it inhibits the molecule that is one step before thrombin is made. It is a once a day medication, whereas Pradaxa is twice a day.
The population of this clinical trial was very unique. This was a high-risk population in that more than half had experienced a stroke previously, and thus rivaroxaban protected most from additional strokes.
The FDA has just announced a September 8, 2011, hearing of the Cardiovascular and Renal Drugs Advisory Committee to consider whether to recommend the approval of rivaroxaban. Thus, this drug may be the second alternative to warfarin approved in the US for stroke prevention in atrial fibrillation, potentially before the end of 2011.
Dr. Hylek thinks this is a very exciting time for stroke prevention in atrial fibrillation. The anticoagulant drug market is expanding, and additional trials, such as the ARISTOTLE trial for apixaban and the edoxaban trial, could also provide exciting results for the atrial fibrillation community.
View the video (almost 9 minutes):
See other background information about Xarelto and Pradaxa:
- Rivaroxaban comparable to warfarin in preventing stroke and other complications of irregular heartbeat
- FDA Approves Pradaxa as Alternative to Warfarin for Stroke Prevention in Atrial Fibrillation
About Elaine Hylek, MD:
Associate Professor of Medicine, Boston University
Director, Thrombosis and Anticoagulation Service, Boston Medical Center
Dr. Elaine Hylek received her MD from the University of Pittsburgh School of Medicine and a Masters in Public Health from Harvard University School of Public Health. She completed her residency training in internal medicine at Massachusetts General Hospital and Harvard Medical School in Boston, Massachusetts. Dr. Hylek is currently the Director of the Thrombosis and Anticoagulation Service at Boston University Medical Center and Associate Professor of Medicine at Boston University.
For more information, see:
Mellanie True Hills: This is Mellanie True Hills with StopAfib.org. I’m at the Boston Atrial Fibrillation Symposium, and with me today is Dr. Elaine Hylek. She is an Associate Professor of Medicine at Boston University, and has devoted her research career to the study of warfarin and stroke prevention in atrial fibrillation. She is the director of the thrombosis service at Boston Medical Center. Dr. Hylek, you are going to be presenting this morning here at Boston Afib. Would you share with us in the atrial fibrillation patient community what you will be talking about?
Dr. Elaine Hylek: Certainly, Mellanie, and thank you very much for the honor of speaking with your audience and the large number of individuals that regularly follow you at StopAfib.org.
This morning we are going to be talking about stroke prevention in atrial fibrillation. In particular, I’ve been charged with discussing the new novel anticoagulants in the clinical trials. Certainly the RE-LY trial has already been published, and I will talk briefly about that, and in addition, the ROCKET AF trial was recently presented at the American Heart Association meeting in November.
For many patients, taking warfarin can be a challenge. Remember, warfarin really can interact with drugs, it can be affected by illness, like fever and diarrhea, and it can be affected by heart failure. In addition to that, we know that there are certain medications that wreak havoc with warfarin; in particular, amiodarone is one that really comes to mind. There has been a quest, a real drive, to try to replace warfarin with medications that would be easier to take, medications that would not require this constant monitoring of every 28 days.
It’s important to emphasize that for many patients warfarin works fine. Some patients don’t seem to mind coming in and interacting with their physician or the anticoagulation clinic on a monthly basis. There is a fair proportion, perhaps a larger proportion of individuals than we realize, that have also been eagerly and anxiously awaiting some breakthroughs.
The first breakthrough was dabigatran, which is a new "direct thrombin inhibitor," that is a small molecule that directly blocks thrombin itself. The RE-LY study, which is what that particular trial was called, was really quite dramatic in the sense that the investigators and patients studied two doses: a 150 milligram dose twice a day, and a 110 milligram dose twice a day. That 150 milligram dose twice a day was actually shown to be more efficacious than warfarin for preventing stroke, which is a huge finding. In addition to that, perhaps the most remarkable finding of the RE-LY trial was that both doses of this drug actually decreased the incidence of intracranial hemorrhage, which is absolutely the biggest fear that doctors and patients have with anticoagulants or blood thinners. Let’s at least put that into some context because intracranial hemorrhage is a relatively rare or infrequent complication so as not to frighten people away from taking blood thinners.
Also important to appreciate, is that the 150 milligram dose of this new agent, dabigatran, as I just stated, was better, or more efficacious, on the stroke side, and in addition, on the intracranial hemorrhage side, but that 150 milligram dose did have an increased risk of gastrointestinal bleeding compared to warfarin. I think as patients discuss these new drugs that are now FDA approved—dabigatran was FDA approved on October 19, it’s called Pradaxa in the marketplace—that these will be discussions that the patients will need to have with their internist, their family doctor, or certainly their cardiologist and really come to some conclusion together about whether or not these new agents would be right for the patients. Again, no monitoring, which I think will be a really attractive feature for a lot of individuals.
I am also going to be talking this morning about the ROCKET AF trial. This was a trial of about 7,000 patients who were randomized to rivaroxaban. This is a little bit different of a molecule; it inhibits the molecule that is one step before we make thrombin, so again, it is different from that standpoint. The rivaroxaban was actually a once a day medication.
Rivaroxaban very convincingly showed that it was non-inferior to warfarin. This was a positive trial, and very important to appreciate that the ROCKET AF trial population was at much higher risk than the RE-LY trial population, and quite frankly, much higher risk than almost any antecedent trial in atrial fibrillation up until the present time. I really have to applaud those investigators and the patients that enrolled because upwards of 50 percent or 55 percent of these patients had had a prior stroke. These patients were willing to be randomized to an experimental drug, which I really applaud. This is how we move science forward.
Again, rivaroxaban…I think the ROCKET AF trial convincingly showed that it was noninferior, or as good as warfarin. When they looked at the population that stayed on the drug, and on their "per-protocol population", there was a suggestion certainly of it being superior to warfarin, but I would say perhaps not as convincingly as the RE-LY trial, but there are many explanations for that.
So, in summary, I think it's fair to say that this is a very exciting time for stroke prevention in atrial fibrillation. We still have the apixaban trial, which is called ARISTOTLE, that will hopefully be published, or the results presented, at the European Society of Cardiology meeting in August or September 2011. We also have edoxaban, another very exciting drug that is being tested in two doses.
Before we end this interview this morning I did want to emphasize that the Food and Drug Administration did approve Pradaxa. But it is important to appreciate that it was the 150 milligram dose that the FDA approved, accompanied by a 75 milligram dose that is really relegated to individuals with significant kidney impairment (or renal impairment). So that the 110 milligram dose, which actually seemed safer, with less bleeding, the Food and Drug Administration did not give that one the green light. Still, a very important addition. I would encourage patients to sit down and read as much as they can, and visit this StopAfib.org website because that would be a very fruitful place for resources to figure out which drug may fit you best. Thank you.
Mellanie: Thank you, Dr. Hylek, for taking the time to speak with us today. From Boston Atrial Fibrillation Symposium, this is Mellanie True Hills reporting for StopAfib.org. Thank you.
Disclaimer: At the time of publication, some companies making products mentioned in this interview are StopAfib.org donors while others are not.