NOACs in the Anticoagulation Space - Episode 2
Manesh Patel, MD: Bernard, 1 of the things I wonder a lot about you could help us with, because I know you’ve thought a lot about it: the mechanism by how these patients with atrial fibrillation [AFib] are developing stroke. Some of it might be atrial fibrosis or a clot or other mechanisms. What are your thoughts on that?
Bernard J. Gersh, MBChb, DPhil, MACC: Thanks, Manesh. I think it’s sort of all of the above.
To get back to your question about the pathophysiology of atrial fibrillation, I think we all agree that a thrombus in the left atrial appendage is probably the most powerful putative cause of thromboembolic stroke in atrial fibrillation. What leads to that is interesting, and I don’t think of atrial fibrillation as 1 disease. I think the 40-year-old athlete with paroxysmal atrial fibrillation has a disease that triggers in the pulmonary veins, and they respond to pulmonary vein isolation ablation.
That’s not the same patient as the vast majority of people we see—70%, 80%, 90% of the population we see. They’re much older, and they do have triggers from the pulmonary vein. But they have a disease substrate, including the atrial appendage and the left atrium itself. And what we’ve thought about and looked at over the last 15, 20 years—and I think the data are pretty consistent—are the common risk factors for atherosclerosis, particularly age and hypertension. But for the other atherosclerotic risk factors, I think of atrial fibrillation as the final common pathway of a vascular disease. These conditions increase arterial stiffness. As a result, when it’s diastolic dysfunction, and this ultimately results in an enlarged left atrium, and an enlarged left atrium is electrically vulnerable.
The clue to ultimately containing the epidemic is controlling risk factors in the community, and I think we will see a leveling off or maybe even a decline in atrial fibrillation. There is quite a school of thought that now feels that when you counsel a patient with atrial fibrillation, risk-factor modification is an important part of it, not just the EP [electrophysiology] component.
Manesh Patel, MD: Yeah, certainly as Prash Sanders and others have published that.
Bernard J. Gersh, MBChb, DPhil, MACC: Absolutely.
Manesh Patel, MD: They’ve shown us that potentially reducing the risk factors helps with that for sure. One more question for you before I go to Dr Califf about how we thought about these trials. How much AFib does someone need to be at risk for these stroke events we’re talking about? This is asked a lot among us.
Bernard J. Gersh, MBChb, DPhil, MACC: I haven’t the faintest idea. Not only that, neither does Professor Granger or you. From a clinical standpoint, I really think the whole issue of subclinical atrial fibrillation and its duration and who should be anticoagulated is 1 of the most interesting and hard topics in the field. Right now if I saw a patient with subclinical atrial fibrillation, it’s picked up on a pacemaker or an ICD [implanted cardioverter-defibrillator] interrogation.
Manesh Patel, MD: Or a watch.
Bernard J. Gersh, MBChb, DPhil, MACC: Or a watch. If it’s 24 hours of atrial fibrillation, that to me is clinical AFib. Between 12 and 24 hours of atrial fibrillation, which would mean if you see it on a watch, you’re going to have to do some other kind of monitoring, I think that’s up in the air. But if they had a high CHA2DS2-VASc score, and I thought there was a high stroke risk, I would probably treat that patient at the moment with oral anticoagulants. I think 0 or 6 minutes, which is the low cutoff to 12 hours, no one knows. And there are 3 trials ongoing. I think if I saw a patient in that range, I would enroll them in 1 of 3 ongoing trials if I could.
The other thing to remember about subclinical atrial fibrillation: it’s not a static entity. There are pretty good data that you may see a patient and they may have multiple episodes of 10 minutes each or 20 minutes. A significant number of them will progress, and they will go from short durations to much longer durations. It’s also associated with heart failure. I think if you make the diagnosis of subclinical atrial fibrillation, the duration is not long enough to warrant oral anticoagulation. It doesn’t mean you shouldn’t look at it again.
Manesh Patel, MD: Follow the patient closer.
Bernard J. Gersh, MBChb, DPhil, MACC: Follow it closer.
TRANSCRIPT EDITED FOR CLARITY.