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I'm Sid Patel from the Timmy Study Group in Brigham and Women's Hospital. Uh, and for this session, we'll discuss implementing evidence-based risk ratification strategies to optimize thrombosis prevention and management in atrial fibrillation, acute coronary syndromes, and for secondary stroke prevention. These are my disclosures. So as an overview for our learning objectives, we'll talk about applying some of the clinical risk scores, including the CHADS VSC as well as the HAS Blood scores to accurately identify atrial fibrillation patients at high risk of stroke and to determine appropriate anticoagulation therapy. We'll also utilize validated risk assessment tools to individualize antithrombotic treatment decisions, and acute coronary syndromes, as well as secondary stroke prevention. Uh, and lastly, we'll touch on improving detection of atrial fibrillation to allow for a timely initiation of anticoagulation. So we'll start with a case of a 65 year old gentleman with hypertension, diabetes, and hypercholesterolemia who presents with chest pain and new atrial fibrillation. He's found to have a non-ST elevation MI and undergoes a PCI of the left anterior descending artery. So now the questions are, what should his antithrombotic regimen be prior to discharge when he's seen again in clinic, and how should that evolve over the course of subsequent follow-up visits over the course of the next year. And so we'll keep this case in mind as we dive in through the next slides. So I think this is likely no surprise to most practicing clinicians. Atrial fibrillation is by far the most common sustained arrhythmia encountered in practice, with a global prevalence estimated at over 50 million, and with 1 in 3 individuals expected to develop atrial fibrillation in their lifetime. Of course, the most feared complication of atrial fibrillation is the risk of stroke. We know from data dating back several decades that the presence of atrial fibrillation is associated with a fivefold increase in the risk for stroke. Such that beyond rate control or rhythm control, as well as management of comorbidities, anticoagulation really is the mainstay of therapy. We know from data from the era of the warfarin versus placebo controlled trials that anticoagulation is actually highly effective in reducing the risk of thromboembolism in patients with atrial fibrillation. These are data which pool all of the warfarin versus placebo controlled trials in atrial fibrillation, and here you can see that warfarin actually resulted in a 64% reduction in the risk of stroke in patients with atrial fibrillation. So warfarin is incredibly effective in preventing the risk of stroke in these patients. So over the last 15 to 20 years, direct oral anticoagulants have really emerged as a preferred option for anticoagulation over warfarin. Not only are they more convenient for patients without the need for routine monitoring, they also have markedly fewer drug, drug, or dietary interactions, and they're also incredibly safer. In meta-analysis of the pivotal DAC versus warfarin trials in atrial fibrillation. The Dox were proven to be at least as effective for prevention of stroke as warfarin, but importantly, there was a marked 50% reduction in the risk of intracranial hemorrhage, a commonly fatal complication of anticoagulant therapy. There was this reduction in intracranial hemorrhage that actually translated to a 10% reduction in all-cause mortality. The advantage of DAx for reducing severe types of bleeding, uh, is not as evident. Um, while they tend to reduce major bleeding in general, they do increase the risk of gastrointestinal bleeding by 25%. And really that's thought to be because each of the four DA is actually active within the GI tract, whereas warfarin actually undergoes first-class metabolism within the liver. Of course, clinical decision-making regarding anticoagulation is on the basis of the annualized risk for thromboembolism, and this will vary for, from one patient to another that has atrial fibrillation. Um, most are likely familiar with the CHADS Vask score. This is really the, uh, risk ratification tool that's used to determine, uh, decision making around anticoagulants in clinical practice. Um, here are the components on the left that go into that score. Um, prior history of heart failure, hypertension, uh, age, whether it be age 65 to 74 years, that gets you a point, or an age above 75 years, uh, diabetes, prior thromboembolism, that gets you 2 points, uh, or a prior vascular disease. Um, sex category, particularly being female, actually gets you a point within the CHAD's vast, but there has been a movement away. Uh, uh, from using this and just going off the CHAD's BA score without the sex category. Uh, these are largely felt to be equivalent given that, uh, sex is actually an age-dependent, uh, uh, risk modifier as opposed to a, uh, intrinsic risk factor. Um, and as you can see when we apply the CHADS mask, there's a stepwise increase in the risk for, uh, stroke per 100 patient years. Uh, and so, you see here on this bar chart that uh Chad's VST score of 2 or greater translates to an annualized stroke risk of 2% or greater. And really that's the basis that informs the guideline recommendations. Um, so if we look at the clinical practice guidelines for atrial fibrillation, uh, whether the American guidelines or the European guidelines, there's a Class 1A recommendation. For anticoagulation of patients with a CHADDS VSC score of above 2 in men or 3 or greater in women, or if you're using the sex agnostic score, just the CHADS VA, a score of 2 or more in the European guidelines, uh, that isn't sufficient for initiating oral anticoagulation. Uh, for patients with a CHADDS, uh, VSC score or a CHADS VA score that's lower, Um, really shared decision making, uh, uh, along with, um, considering other risk enhancers for stroke or systemic thromboembolism is, is recommended as a two-way recommendation to, uh, guide decision making regarding anticoagulation. Of course, with any anticoagulant therapy, there's always a trade-off in bleeding risk. And to that end, many risk scores have been developed to predict anticoagulant-related bleeding. The most common of which is the HS-Blood score. Uh, here are all of the components that go into the HS-Blood score, uh, factors such as hypertension, uh, presence of abnormal, uh, renal or liver function, a history of stroke, as well as history of prior major bleeding. A label INR for patients uh treated with warfarin. And again, the Halo score was actually specifically developed to predict uh bleeding for patients treated with warfarin. Uh, age is also a risk factor here, uh, as well as use of uh alcohol. Uh, as well as use of alcohol or drugs which increase the risk of bleeding. Uh, and as you can see, the HA blood score actually does a, a modest job of, uh, predicting bleeding in patients treated with warfarin. That's shown here on the right where you see with higher H blood scores, there's a higher risk for major bleeding. Given that the majority of patients now, particularly in the United States, are treated with direct oral anticoagulants, uh, the DOAX score was developed to predict DOAC-specific bleeding. But the one thing to emphasize here is that many of the risk factors you see that are specific both to the HAS blood or the DAC score overlap with those used to predict thromboembolism in the CHA's vasc, right? So factors such as age, uh, factors such as prior stroke or a history of systemic embolism, uh, diabetes or hypertension. That it becomes really hard to separate patients who are high ischemic risk from those who are high bleeding risk. And really that's the reason that clinical guidelines do not recommend the use of bleeding scores to make decisions on starting or withdrawing oral anticoagulation because the risk factors for thromboembolism and bleeding commonly overlap. And it's also important to note that the sequelae of stroke differ markedly from bleeding, which may be transient, uh, may stop with temporary interruption of anticoagulation or with local measures to address, uh, the site of bleeding. However, bleeding risk scores may be useful in assessing modifiable risk factors, such as alcohol, for example, or the use of concomitant antiplatelet therapies that may or may not be indicated. Uh, we talked a little bit about the CHADS task as well as the Halo score. Um, but it's important to know that these risk scores actually have overall quite modest discrimination for, for predicting who's actually going to go on to have these events. Um, and so, uh, newer data has shown that incorporating some of the clinical risk factors we discussed along with, um, cardiac biomarkers that are routinely assessed, such as the natriuretic peptides or cardiac troponin can actually enhance risk ratification. And uh further inclusion of novel biomarkers, as well as uh echo parameters, left atrial size, left atrial strain, really markers that look at atrial remodeling, um, could improve risk ratification. And so, uh, particularly in the era of contemporary electronic health records and advances in, in, in, in machine learning, um, much of this may make its way into, into clinical practice in, in the near future. Um, switching gears a little bit, uh, uh, there's, it's, it's worth noting that, um, 1 in 4 patients who actually present with a stroke actually have no identifiable etiology. And so a common question that arises is that a proportion of these patients actually have likely occult atrial fibrillation that has never been detected. And so, um, is there a role for mass population screening to detect atrial fib