Transcription:
New Study on Wearables for Stroke Prevention in Patients With Atrial Fibrillation

Melanie Cole (Host): Welcome to Better Edge, a Northwestern Medicine Podcast for physicians. I'm Melanie Cole. And joining me today is Dr. Rod Passman. He's the director of the Center for Arrhythmia Research at Northwestern University Feinberg School of Medicine, the Jules J. Reingold Professor of Electrophysiology and Professor of Medicine in the Divisions of Cardiology and Preventive Medicine at Northwestern Medicine. Dr. Passman is here today to discuss the rhythm evaluation for anticoagulation of atrial fibrillation or REACT-AF trial. And Northwestern University and Johns Hopkins University were recently awarded a 37-million grant by the National Heart, Lung and Blood Institute to conduct this seven-year trial. The study will use Apple Watches and a specifically developed app available on iPhones to create a personalized care for each patient.

Dr. Passman, thank you so much for joining us. I'm so psyched about this podcast today. I'd like you to start by telling us a little bit about your role at the Northwestern University Center for arrhythmia research and the goal or the focus of that center. Let's get into that part of the topic first.

Dr Rod Passman: Well, first of all, thank you so much for having me. I really do appreciate this opportunity. So, the Center for Arrhythmia Research really tries to leverage all of the amazing things going on in arrhythmia research throughout Northwestern University, not just from the heart rhythm specialists, like people like me, but there are people in the school of engineering, people in epidemiology, people in radiology, all doing work that pertains to the treatment of heart rhythm disorders.

So, the purpose of the center is to sort of combine these talents and resources towards a shared goal. So, we work on projects together. We write papers together, we write grants together. And really, I think amazing things happen when you get out of your silo, when you cross-pollinate across this excellent institution.

Melanie Cole (Host): Well, I certainly agree with you. Now, tell us some of the challenges that have remained in predicting stroke risk in atrial fibrillation patients and some of the complications with the current standard of care, because that seems to be what this is all about.

Dr Rod Passman: Right. Well, you know, the first thing to recognize is that the abnormal rhythm we're talking about, atrial fibrillation, is the most common sustained rhythm in adults. So if you're a 40-year-old male or female, and you are lucky enough to live to your 80s, you have about a one in three chance of developing AFib in your lifetime. So, this is incredibly common. It's probably about 10% of the population over age 65 that we know about. And while atrial fibrillation may have many symptoms, many people are completely unaware that they have it. But whether you feel it or not, the major risk of AFib is stroke. These tend to be major strokes. These tend to be strokes that are severely debilitating or life-ending.

So, we have a method of trying to estimate stroke risk, but it's not really very good. And what winds up happening is that pretty much 80% to 90% of the millions of people with atrial fibrillation across this country and the tens of millions of people with this rhythm disorder across the world are recommended to be on blood thinners called anticoagulants. So, anticoagulation has been the standard of care for the last, you know, 25 years. Certainly, that's changed over the last 12 years or so with the introduction of these novel or direct oral anticoagulants. But the bottom line is, is that these drugs, while highly effective at reducing the risk of stroke, also carry a risk of major bleeds and minor bleeds. And what happens is, is that many patients who should be on anticoagulation therapy are never prescribed it. And when they are prescribed it, maybe have to stop within a year or two because of real perceived risks.

Melanie Cole (Host): Such an interesting challenge and topic we're discussing today. And congratulations, Dr. Passman, on receiving the first ever National Heart, Lung and Blood Institute grant to study wearables for stroke prevention in patients with atrial fibrillation. I'd like you to tell us about the grant. But before you do that, how did it come about? And the collaboration with Hopkins is fascinating.

Dr Rod Passman: So, I'm a clinician, right? I spend a lot of my time taking care of patients. And this issue kept coming up where people questioned, you know, why they're taking an anticoagulant every single day of their life when we did an ablation on them or they're on medication, and every monitor and every EKG that we have done showed a normal rhythm.

Now, that question really made me think that we have sort of a one-size-fits-all model where we treat all patients the same, regardless of how much atrial fibrillation they have, and regardless of whether those patients are sort of the recipient of a successful rhythm control strategy. And the reason is because AFib is often silent and the drugs that we give to patients and the treatments that we give them are rarely a hundred percent effective. So, how do we know that it's safe to stop a blood thinner when you may be having ongoing episodes of AFib that you may be unaware of?

So, the current treatment guidelines say that you are on a lifetime of anticoagulation, regardless of whether you're in AFib every minute of the day or regardless of whether you have one episode a year or don't have episodes anymore because you've had an ablation done or on drugs. So, that doesn't make a lot of sense to me.

I then saw a patient maybe going back about 15 years ago, who had an intracranial hemorrhage on anticoagulation. This was a life-changing event. He never worked again a day in his life, was wheelchair-bound, functioned as a lawyer before this, and he was on an anticoagulant even though his atrial fibrillation was well controlled. So, really at that time I thought, "Well, why can't we target this therapy, right?" Why can't we give anticoagulation only in response to a prolonged episode of atrial fibrillation and give it only for maybe a few weeks? Or a person who had one episode of AFib a year would only need to be on anticoagulation maybe for a few weeks out of the year. And the patient who never has AFib anymore because they've had a procedure done or on effective therapy, maybe we can spare those patients through risks of anticoagulation while still protecting them against stroke.

Melanie Cole (Host): Wow. This is absolutely amazing what you're doing and recent advances, Dr. Passman, in device technology. Boy, they're moving so fast. And drug therapy, they really have the potential to change the way investigators manage atrial fibrillation. So now, tell us about the rhythm evaluation for anticoagulation or the REACT-AF trial, how it's related to the grant and the aim of this pilot study.

Dr Rod Passman: Well, so we need to go back a little because when we first started to think about this, we didn't have wearable technology like we do today that can sense abnormal rhythms of the heart. So, the pilot studies that we did used implantable devices. You can use a pacemaker or you could use a device called an implantable cardiac monitor that can collect data on atrial fibrillation, and we can use that to sort of target the anticoagulation therapy. The problem with that is that this is expensive technology, it's invasive technology, and it requires a staff like we have at Northwestern to receive that data from these medical devices and then sort of get back to the patient in almost real time.

So while those pilot studies established the feasibility of what we're doing, they weren't scalable for the millions of people who might be candidates for this approach? So, I think the two big breakthroughs were as, as I alluded to earlier, when these new blood thinners came out, one of the big advantages of them is that they would anticoagulate you in a couple of hours as opposed to Coumadin, which would take four or five days. So now, that we have medications that could rapidly anticoagulate you, then what we needed is a warning system to alert you as the patient that you're having an episode of AFib, and allow you to restart your blood thinner only during that high risk period. So, wearable technology for atrial fibrillation is relatively new. It began with a device called Cardio Band, maybe five years ago. And as you know now, Apple and Fitbit and Samsung and so many other companies are in this space. And it really took that combination to move this from a fantasy phase to a testable strategy.

Melanie Cole (Host): So, I'd like to get into that just a little, because it's so exciting that together these advances can allow for that continuous atrial fibrillation monitoring with that targeted anticoagulation only around the time of an AF episode, which is what you just described, and thereby reducing that risk of the drug-induced hemorrhaging, and that is what patients get worried about and other providers. But now, tell us how the involvement of Apple and Apple Watch in the grant got involved and Hopkins and tie this all together for us.

Dr Rod Passman: So, a study of this magnitude doesn't happen in isolation. I'll tell you that an NIH grant, a clinical trial of this magnitude, requires a clinical coordinating center, and that's Northwestern, and a data coordinating center, and that's Johns Hopkins. And Johns Hopkins came to us through the Trial Innovation Network, which is an NIH-funded network of academic institutions whose goal is really to discover new ways to do clinical research in a more efficient manner. So, we were really quite fortunate to team up with Hopkins because they have great experience and really add so much expertise to the table of how you establish a data coordinating center for a national trial of this magnitude.

And then, the Apple story is an interesting one. We had some contacts. We went out to Apple and pitched this idea. And that's a whole story in of itself because Apple is a consumer electronics company. And while they make these interesting technologies that could be used for medical treatments, where they fit in and where they see themselves is, I think, still emerging. They sell millions and tens of millions of devices, and any one disease is a relatively small market for them. But more importantly, medical research and medical treatment has risks that pharma companies and medical device companies are willing to take. And whether consumer electronics companies want to get into that business, I think, is still a little murky.

So, through many years of discussion with Apple and advances in their technology, it's sort of dovetailed nicely. You know, they developed watches that can sense episodes of atrial fibrillation that can tell you how much atrial fibrillation you have. And this partnership was forged in part with the assistance of the American Heart Association. And I think together, we've worked out a path forward where we will use this technology, customize for the purposes of the study that we're doing, and they're providing not only the hardware for the study, but a lot of the technical expertise needed to do something like this.

Melanie Cole (Host): So complex. Take us from bench to bedside, Dr. Passman. How might the results of the REACT-AF trial benefit patients in the future? Tell us about what you see happening, whether FDA has to get involved. How does this work and what do you see on the horizon for this?

Dr Rod Passman: We have designed a trial that is largely pragmatic and we're building all the software and APIs and all that necessary to make this readily available should it be a positive study. So, what I foresee is that if the study is positive, that we may take lots and lots of patients who are currently treated with daily oral anticoagulation and move them to this pill-in-pocket approach. And my hope is that this is such a cost effective strategy because not only are you saving the cost of buying your medications every day, but you're saving the cost of the bleeding events, which can be quite expensive if they require hospitalization.

So, my ultimate hope is that an insurance company would recognize this and then realize it's cheaper to buy a smartwatch for you than to pay for daily oral anticoagulation and the risks of daily oral anticoagulation. So, I think that this will be a pretty quickly adopted strategy for what we perceive as half the population with atrial fibrillation, so potentially millions of people.

So, the FDA has already opined. We're using these oral anticoagulants in a way that they are not currently approved. So, we have what's called a waiver of an IND from FDA. And the device issue is also currently under discussion about whether that needs to be regulated. The algorithms that we're using are based on two FDA-cleared algorithms in terms of AF detection. So, we're currently in discussion with the FDA as to whether what's called an IDE is also needed.

So, as you alluded to earlier, a study that uses digital health like this really requires a lot of thought and interactions with entities and companies that aren't necessarily usually in this ballgame. So, it's been challenging and very illuminating, I would say.

Melanie Cole (Host): And exciting, Dr. Passman. So exciting. It's really such an advancement in medicine and could affect so many millions, as you say, patients. As we get ready to wrap up, tell us a little bit about recruitment, when that will start for the trial, and anything you'd like other providers to know, the unique features on how the REACT-AF trial is being performed, how it might impact research in the future. Wrap it all up for us.

Dr Rod Passman: So, recruitment is going to begin in late spring of 2023. These are patients who are on the lower end of the risk scale for strokes, so we're talking about CHA2DS2-VASc scores of 1 to 4. Patients will be given a free study-specific Apple watch, but they need to own an Apple phone to be in the study because the watch needs to be compatible with the phone.

I think one of the big advantages of this study is that the only touch that you have with the patient will be at the time of enrollment. All other followup is done remotely through the phone. So, patients will be sent questionnaires. We'll be using something called geofencing, which will alert us if someone's been hospitalized, and we can then get those medical records. So, I think not only are we asking a really fascinating question, but the way we're asking it and the way we're using technology to follow these patients over the three to five-year timeframe of the trial, I think, will make future research much more cost effective and efficient.

Melanie Cole (Host): Dr. Passman, please come back on and update us as this trial begins and you're starting to see some of those positive results that I fully expect you will see. Thank you so much. What an exciting time to be in your field. And to refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/cardiovascular to get connected with one of our providers.

That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. Please remember to subscribe, rate, and review this podcast and all the other Northwestern Medicine podcasts. I'm Melanie Cole.