Dr. Daniel Singer Discusses Atrial Fibrillation Stroke Prevention and Anticoagulants — Video

Dr. Daniel Singer Discusses Atrial Fibrillation Stroke Prevention and Anticoagulants — Video

By Mellanie True Hills

  • Summary: In this video interview, Dr. Daniel Singer discusses devices and anticoagulants for atrial fibrillation stroke prevention, including the rivaroxaban and dabigatran clinical trial results.
  • Reading and watching time: Approximately 11–12 minutes

In this video interview, Dr. Daniel Singer, of the Harvard Medical School and Harvard School of Public Health, discussed topics covered in the stroke prevention in atrial fibrillation symposium he moderated at the Boston AF Symposium 2011. The topics discussed included the RE-LY trial of dabigatran, the ROCKET AF trial of rivaroxaban, and devices for keeping clots from forming in the left atrial appendage of the heart.

View the video (10 minutes):

About Daniel E. Singer, MD:

Professor of Medicine, Harvard Medical School
Professor, Department of Epidemiology, Harvard School of Public Health
Chief, Clinical Epidemiology Unit, Massachusetts General Hospital

Dr. Singer is an internationally recognized leader in the field of stroke prevention in atrial fibrillation (AF). With his colleagues, Dr. Singer has helped establish the efficacy of anticoagulant therapy in AF, identified risk factors for stroke, and defined the optimal range of anticoagulation in AF. He was the chair and lead author of the Atrial Fibrillation chapter in the 2008 American College of Chest Physicians Consensus Conference on Antithrombotic and Thrombolytic Therapy. He has also conducted extensive investigations into the impact of hyperglycemia, impaired glucose tolerance, and diabetes on the development of vascular disease.

Dr. Singer was the 2003 recipient of the John M. Eisenberg Award, the Society of General Internal Medicine’s highest award for career achievements in research. In addition, Dr. Singer was awarded the 2008 C. Miller Fisher Award from the New England chapter of the American Heart Association/American Stroke Association for his research on stroke prevention. Dr. Singer also received the 2007-2008 Harvard Medical School William Silen Lifetime Achievement in Mentoring Award.

See Dr. Singer’s profiles and contact info:

Video Transcript:

Mellanie True Hills: This is Mellanie True Hills from StopAfib.org. With me today is Dr. Daniel Singer. He is a Professor of Medicine at Harvard Medical School, and Professor in the Department of Epidemiology at the Harvard School of Public Health. He is also chief of the Clinical Epidemiology Unit at Massachusetts General Hospital. He has just conducted a mini-symposium here at Boston Atrial Fibrillation Symposium today. Dr. Singer, thank you for joining us. Would you share with us what you covered in the Symposium this morning?

Dr. Daniel Singer: Mellanie, it’s my pleasure. This is a very exciting time in stroke prevention for atrial fibrillation. First let me alert the viewers that I have some potential conflicts of interests, which are that I consult for many of the pharmaceutical companies producing new anticoagulants, and I was on the executive committee of the ROCKET AF trial of rivaroxaban.

Today’s session reviewed what we know about warfarin to prevent stroke in atrial fibrillation, and we are learning so much. In addition we now have alternatives to warfarin that are much easier to take, that appear to be as effective, if not more effective, and potentially safer. Those were the main points we covered in the sessions today. In addition, we talked about alternatives to drugs to prevent stroke and atrial fibrillation. Those are mechanical ways of blocking the left atrial appendage.

The most important points to recognize are that warfarin, if it is managed properly — that usually means the time in therapeutic range (that is, your time in the INR range of two to three), if you can be there 60+% of the time — you have excellent protection against stroke and you probably have a very low risk of any devastating outcome from warfarin. So, warfarin is a very good drug, particularly when it is managed by organized anticoagulation management services.

That said, lots of people don’t want to get the INR testing on a frequent basis, don’t like adjusting their dose, and there is a fraction of individuals who, no matter what, can’t control their INR appropriately. For those individuals we have excellent news, there are now several targeted oral anticoagulants that are proven to be as good as, or even better than, warfarin.

The most important information is that the RE-LY trial of dabigatran, which is a direct thrombin inhibitor, the RE-LY trial has demonstrated that dabigatran twice a day in the dose of 150 milligrams, and in the dose of 110 milligrams twice a day, is as good as warfarin and probably a little safer. The 150 milligram dose produced evidence that it might be actually superior to warfarin, which is truly remarkable. This drug was approved by the FDA in October [2010], and in the United States now, in Canada, and I don’t believe yet in Europe, is available for patients. It is a twice a day drug, it provides excellent protection against stroke, and adds very little in the way of bleeding risk. There are issues with regard to who is going to pay for it, and those are being worked out with the insurance companies at this time.

Not everybody needs to be taking an anticoagulant, so you need to confer with your physician whether your risk of stroke is high enough to merit taking an anticoagulant, because even the new anticoagulants, which are proving to be safer, pose dangers in terms of bleeding.

Dabigatran is now available — the RE-LY trial had spectacular results.

The next important item to note is that the rivaroxaban trial, the ROCKET AF trial — I’m a member of the executive committee of that trial — is finished. It’s another enormous study — 14,000 patients with atrial fibrillation around the world — of rivaroxaban 20 mg a day versus warfarin with a targeted INR of two to three. The analysis, which hasn’t been published but was presented at the American Heart Association, indicates that it is non-inferior — that is a technical term meaning that it is as good as warfarin in preventing stroke in atrial fibrillation. Actually, the stroke rates were in fact a little lower, but statistically speaking the claim can be made that it is “noninferior”, it is just as good as warfarin in protecting against stroke. And it also, although the overall bleeding rates were about the same as warfarin, just like dabigatran it has a lower rate of intracranial hemorrhage. That is the type of bleeding, into the brain, or around the brain, that is so dangerous, and those rates, which are low to begin with, are clearly lower in the new anticoagulants, dabigatran and rivaroxaban. Rivaroxaban we won’t hear from the FDA for a while on this, and the formal manuscript will be published, I assume, in the next six months.

That’s not the end of the story. There are many other so-called direct thrombin inhibitors and direct Factor Xa (10a) inhibitors that are very targeted anticoagulants as compared to warfarin, which inhibits the effect of many parts of the coagulation pathway. These targeted direct thrombin inhibitors and Factor Xa inhibitors are in massive randomized trials and we know that in several instances they have achieved their recruitment goals, and now are following patients to accumulate the data to determine whether they work.

I think it’s a great time for stroke prevention in AF. I think we’re going to have multiple choices of easier-to-take medicines, no need for monitoring, good consistent anticoagulation regardless of diet and regardless of other drugs that you are taking, and we’ll have a choice — and in 2-3 years we’ll have multiple choices — and right now we have dabigatran as an alternative to warfarin.

Let me make a comment about who might go onto dabigatran, and this was a point of discussion in the meeting. If you’re doing very well on warfarin, if your time in therapeutic range is high, 70% or more, the benefits of going onto dabigatran are small. On the other hand, if your time in therapeutic range is less than that, particularly if it is a low value like 50%, then you really should think about switching to a more consistent anticoagulant. Again, we’re all concerned about what the cost implications are, and you have to check with your insurer and you have to check with your pharmacy about how much this is going to cost you because it can be quite expensive.

That’s the really striking good news from 2010 and going forward for a year or two.

Mellanie: I definitely want for us to talk a little bit about the devices as well.

Dr. Singer: If you think about what causes stroke in atrial fibrillation, we now know that it is clots in the left atrium that result from the fact that when you have atrial fibrillation the left atrium doesn’t contract appropriately, and there is a little pouch on the left atrium, called the left atrial appendage, and that seems to be the primary source of clots in standard, so-called non-rheumatic atrial fibrillation.

You might think, “Why do I have to anticoagulate everything in the body? All I need to do is to take care of that left atrial appendage.” That is the motivation behind developing devices to either occlude the left atrial appendage, or remove the left atrial appendage. There’s data on something called the WATCHMAN device. There has been a large trial, not a trial of the magnitude the drug makers use — a tenth the size of those —but which is suggestive that it may protect against stroke. We need to collect lots more data, but the idea is very elegant. It might potentially be a one-time solution to the problem of stroke prevention in atrial fibrillation, but for right now that is just research. The most important point is that if you’re at a high enough risk to need anticoagulants — you have to talk to your doctor about that — then you either take warfarin or you could take dabigatran, and look forward to the other alternatives.

Dr. Reddy, of Mt. Sinai, gave us a nice discussion of other devices. There are two or three devices that are really elegant that are being developed that can be done through catheters and other minimally invasive approaches to take care of that left atrial appendage, to basically block it off and then have the body heal and put fibrosis tissue around it, so there’s no more left atrial appendage, no place for those clots to form. That’s exciting, but again, that I think is years away from settling definitively.

Mellanie: Dr. Singer, thank you so much for sharing with us an overview of what was covered today at Boston Atrial Fibrillation Symposium in your mini symposium on stroke prevention. For StopAfib.org, this is Mellanie True Hills. Thank you so much.

Dr. Singer: Mellanie, it has been a pleasure.

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