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Welcome to the Quick Consult podcast brought to you by Medall. Before starting this podcast, please review the faculty information, disclosure statements and learning objectives using the link in the episode description. To claim your CME credit, complete the evaluation using the link in the episode description. This podcast is a continuing education activity managed and accredited by Current Concepts Institute in collaboration with Metall. This activity is supported by independent medical education grant from Johnson and Johnson and Bristol-Myers Squibb. Welcome to Voices in Thrombosis, a metal educational series designed for healthcare professionals. I'm your host, Doctor Phil McElnay, and over the next two episodes, we'll be bridging the gap in thrombosis management for patients with atrial fibrillation, acute coronary syndrome, and those needing secondary stroke prevention. This podcast is brought to you by Medal in joint providership with Current Concepts Institute, and you can read the CME material associated with this event at Medal Education.com. Today we're honored to have Doctor Christian Ruff with us. Doctor Ruff is the Director General, uh, Director of General Cardiology at Brigham and Women's Hospital, a senior investigator in the TIME Study Group, and an associate professor at Harvard Medical School. His work focuses on atrial fibrillation, risk stratification, and antithrombotic therapy. Doctor Ruff, thank you so much for joining us. Thank you, I really appreciate it. Uh, to start, could you set the stage for our listeners? Why is effective thrombosis management in conditions like atrial fibrillation so critical? Yeah, it's a, it's a great question. And obviously, atrial fibrillation is very common, you know, 1 in 3 patients will develop it in their lifetime. And we know one of the biggest issues that we face is those patients, once they're diagnosed, we know that they have an increased risk of stroke, about 5-fold that of other individuals their age. And these strokes are the worst types of strokes we see in clinical practice. About a third of them, when they're not on an anticoagulant, are fatal, uh, and many of those who survive have permanent neurologic disability, the loss of the ability to live independently, and that's something obviously our, our patients fear the most. And we know that anticoagulation can substantially reduce that risk by about 60 to 70%. And so really once a patient has atrial fibrillation, we're really focused on do they meet criteria for anticoagulation. The vast majority do, about 90% of patients meet criteria for anticoagulation or being on a blood thinner, and we know blood thinners, if they can tolerate it, will dramatically reduce that risk again, somewhere around 60 to 70%. That really puts it into perspective. When a clinician is faced with a patient with atrial fibrillation, however, they often hear some sort of alphabet soup of scoring systems, right? Uh, Chad's vasque has bled the evolution of those. Could you walk us through what these are and why they're so important in clinical? Yeah, and that's a great question, because once we have a patient, we want to figure out, you know, do they, is their risk of stroke high enough to warrant being on an anticoagulant? Remember the, the downside of being. Being on an anticoagulant is that anytime you prevent clotting you may cause bleeding. So is their risk of stroke higher than their risk of bleeding on the anticoagulant? And the, the short answer is that not every patient needs to be on an anticoagulant. So we don't want to give a drug that has side effects where patients risk is, is low for stroke. But we figured out that really probably about 8 90%, 85, 90% of patients with atrial fibrillation do have a high enough risk of stroke to warrant being on an anticoagulant, even though the anticoagulants cause bleeding. But how do we figure out who are those patients who need it? And they've looked at patients with atrial fibrillation, developed sort of easy to use clinical risk scores of different risk factors that you can kind of count up and. The patient has, say, for one of the most common is the CHAS VAS score, and basically it's an acronym of different risk factors. Do they have congestive heart failure? What's their age? Do they have hypertension, diabetes? Have they had a stroke before, etc. And you can add them up and if you have two or more risk factors, your risk of stroke is high enough to at least consider being on an anticoagulant. And so once you make a diagnosis, you say. What's their age? What's their gender? What are their other risk factors, and you kind of add those up and then you see, do they have two or more? And again, the cut point for anticoagulation in the guidelines is, is about risk factors of 2 or more. And now, obviously we have risk factors to predict stroke, but they're also risk factors to predict bleeding and has bled is one of the most common ones. The problem is many of the factors that predict stroke hypertension, prior stroke, age also predict bleeding. And so one of the issues with the bleeding risk score is a high HS blood, which is generally a score of 3 or greater, is also usually the same patient who has a high CHADS VAS score. So what the guidelines have generally said is if your patient has 2 or more risk factors of stroke, particularly with the CHADS VAS score, you should consider. Indefinite anticoagulation and the Has blood score, even if it's high, shouldn't be used to withhold anticoagulation from a patient, but simply to flag a high bleeding risk to see other things that you could do to lower their bleeding risk. So some of the things in the HS blood score are things that are modifiable. One of them is a labile INR, which is for warfarin. Well, if they have an INR that's all over the place, use a DAC instead of warfarin. Other things there are alcohol use increases your risk of bleeding. Well, counsel, you know, either abstaining from alcohol or using it in moderation, or other drugs that increase the risk of bleeding on an anticoagulant such as non-steroidal anti-inflammatory drugs or antiplatelet therapy. So to use the high blood score to not deny anticoagulation in patients who may benefit, but simply to figure out if they have modifiable factors that you could intervene on to lower that risk. That's a very clear and practical distinction. Now moving to treatment and you've touched on, uh, direct oral anticoagulants or DAX, uh, they've become the standard of care in many cases over, over warfarin. Based on the data, what are the key advantages of DAX? Yeah, and so DAs were studied in 4 large phase 3 trials versus warfarin, and, and really they're all, they're more similar than they are different, and I think one of the important things is they're highly effective. They're as good as warfarin, if not slightly better in reducing ischemic stroke. And remember, warfarin's very good in reducing stroke about. 65-70%. So the DAs are very good in reducing stroke. Their main advantage is that they're far safer with respect to serious or fatal bleeding. Now, most of the serious and fatal bleeding on anticoagulant in the AF indication is intracranial hemorrhage or bleeding in the brain. And if you bleed in your brain on anticoagulant, there's about a 50% mortality to that. And so it's certainly something that we're very scared of and we want to avoid. And the DAs are much better than warfarin resistant bleeding in the brain, reducing that by half, so cutting it in half, and that's really the major advantage of the DAX. And so they're very effective. They reduce fatal and serious bleeding, particularly because they're much safer with respect to intracranial hemorrhage. The issue is compared to warfarin, they're not that much better when you look at all bleeding. Uh, particularly GI bleeding or gastrointestinal bleeding, which is about 2/3 or 3/4 of the bleeds we see in the atrial fibrillation patients. So the DAs are a major advance. There's no real food interactions. There's very limited drug interactions. You don't need to get a blood test to monitor it. Uh, they're much safer with respect to serious bleeding. So it's a major advance. The problem is you still see a lot of bleeding. And that bleeding leads to significant undertreatment of patients, so we do need something better, particularly something effective, but that's safer. The safety profile is important as well as getting the dose correct, and that seems to be a common challenge. What are the dangers of inappropriately reducing a DA dose out of concern for bleeding? Yeah, so what we've seen in what patients had a bleed or someone's concerned about bleeding, either they're not prescribed an anticoagulant or they're not taking it, so they're completely unprotected from stroke. But another strategy that's often used is to give them the lower dose. Now there, there are criteria for all of the DA for a reduced dose, but that. That really is in patients where their clearance of the drug is impaired and so that they're getting a reduced dose, so the level of the drug in their body really is the same as someone who say had normal kidney function because the drugs are all renally cleared. But what some people do is even in patients who don't meet the dose reduction criteria, they have no low body weight or no impaired kidney function to just give them a lower dose intentionally even though they don't qualify. But what that does is that ends up giving them a subtherapeutic dose of the DA. And if you look at most of the studies, what you end up seeing is potentially an excess risk of ischemic events, particularly ischemic stroke, and it doesn't appear to be that much safer. So what we're routinely doing is either not treating.