Thank you, Julia. Thank you, everybody, for being here this evening, and thank you to the case presenters. They really did raise a number of very interesting conundrums that we face daily in our clinical practice. So each of the speakers will be addressing some of these different topics, and my topic today is to talk about underuse and inappropriate dosing of anticoagulation. These are sort of the objectives, and as I mentioned, I'll be talking about the anticoagulation and some of the, not only the complexities and the importance of anticoagulation and atrial fibrillation, but some of the barriers, and I'll be concentrating in particular on an at-risk population that we have to anticoagulate for their atrial fibrillation and why we have to anticoagulate them. So you know the famous CHAZ-VASc score. We know that age and prior embolic events are the two most potent predictors of a subsequent embolic event. So as the CHAZ-VASc score increases, the risk of subsequent embolic event increases, and as you see from the figure on the left, it's not just stroke risk that increases, but AF will increase to 3.6 times the higher risk of other types of embolic events, and that is largely driven by age. So taking all the data together, the class 1 indications or class 1 recommendations are for anticoagulations in patients in particular who are CHAZ-VASc score 2 for men or 3 for women who are needing anticoagulation, and these are our choices, warfarin or one of the DOACs. But putting it all together, and we'll go over some of these data, the NOACs or DOACs as you prefer are receiving a little bit of a higher level of recommendation or preference as you would for anticoagulation in most patient populations. So that's what we'll be concentrating on and how to use these drugs and why we're using these drugs. So I think it's generally accepted that unless contraindicated, anticoagulation should be prescribed for patients with atrial fibrillation who are at risk. It's generally accepted, I think, nowadays that DOACs are superior to warfarin for preventing strokes and are considered treatment of choice in most patient populations. I think you see that up here are the two, and I think our cases that were presented show the two sort of dreaded things, either the hemorrhagic stroke or conversion of an ischemic stroke into a hemorrhagic stroke that are one of the largest concerns that we have in terms of anticoagulation. There are other things that sort of are either barriers that are real or barriers that we put in ourselves as we're thinking about anticoagulation in patients. Clinical variables that are sometimes a little bit hard to pin down. There's a lot of bias in terms of the providers, bias in terms of the patients receiving the anticoagulations. What, gee, doc, what if I fall down? Well, how many times have you actually fallen down? So there's a lot of sort of barriers that get in the way of anticoagulating patients. These things are not trivial, as you all know, as you've tried to take care of these patients. I think another very important barrier that gets in the way of taking care of patients is unfamiliarity on the part of the providers with how to use the different medications. I want to concentrate on the elderly because they are our largest at-risk population, and they incorporate a lot of the other at-risk pieces as we'll go through the rest of this talk. You can see that there are about 5 million people in the U.S. right now who are in atrial fibrillation and are at risk for having a stroke related to their atrial fibrillation, and that risk is going to increase by 2050 by about two and a half fold, and that's largely because the population is going to be aging by 2050. Fifteen to 20% of all strokes are related to the atrial fibrillation, and the stroke risk is inherently higher in the older population. Those are the people who have had prior strokes or prior embolic events. AF-related strokes have a greater degree of morbidity and mortality, and another barrier to treatment in these patients is about a third of them will not even realize that they have atrial fibrillation, so it makes it very hard to appropriately anticoagulate them when neither you nor they realize that they have had atrial fibrillation. Factors complicating the management of anticoagulation in the elderly include some of the things that you've seen on the slides that were presented at the beginning. Multiple comorbidities, the cardiovascular disease, concomitant antiplatelet agents, and thank goodness that's one of, I think it's Dr. Gold who's going to be talking about that, one of you guys is going to be talking about that. A lot of these patients will have concomitant CKD, which independently increases their risk of stroke and bleeding. Frailty is very difficult to determine. What is frailty exactly, how do you measure it, and how do you account for it in your determination of what anticoagulation, how intense your anticoagulation should be? Cognitive impairment, are they going to remember to take their medications? Dependence, are they in a nursing home or a rehab facility? What is really their risk of fall? How many times have they fallen? And polypharmacy and unfamiliarity on our part, really what the interactions with different medications might be. Together these different factors increase mortality, lead to higher admission and readmission rates, and very often will lead to inappropriate dosing and inappropriate use of different medications. So unfortunately the end result, the net result of all of this, is that the people who are at the highest risk are the people who are least likely to be receiving the anticoagulation. The people with the higher CHA2DS2-VASc score are the people who are receiving anticoagulation least frequently. Warfarin, I think we can X that out pretty much at this time, hopefully in the higher risk population, because it's just too complicated to use. Bleeding risk, daily regimen, high nonadherence rate, need for frequent blood tests, the inability to get that done in different facilities or to get to the place to get your blood drawn, just a lot of barriers to use of Warfarin. Somehow in my slides it ate up. There we go. The DOACs are also not free of complications in terms of use. There are bleeding risks related to those drugs, and they are a little bit complicated to think about when you're thinking about doing surgery. There's often a lack in your local ER of some type of reversal agent to be used for a patient who might come in with trauma, and I will say that there is probably high cost and to some degree a formulary bias in terms of what drug will be paid for by the insurance company that that patient may be associated with. So unfortunately these things lead to a high discontinuation rate over time for appropriate anticoagulation, particularly in the elderly, and over time about 25% to 75% of the elderly will not be anticoagulated either appropriately or perhaps at all. So looking at sort of the risk and benefit ratio, yes, indeed there is an increased risk of stroke and there is increased mortality and morbidity related to atrial fibrillation in the older population, and yes, these people do have a lot of potential for harm with anticoagulation, particularly if they've had a prior bleed or some of these other factors have come into play, but the risk of intracranial hemorrhage and fatal hemorrhage remains low as a consequence of anticoagulation, and really the balance does favor ongoing anticoagulation in these patients. So several studies have shown that despite favorable risk-benefit profiles, the main independent factors that lead to not anticoagulating the patient are not the thromboembolic risk, but these other factors such as age itself. Other factors, dependence, cognitive impairment, the sort of difficult to really pin down frailty and risk of falls, none of these alone are absolute contraindications to anticoagulation, but certainly must be weighed in as you are considering anticoagulation for the patient. What ends up happening is that the wrong drug or the wrong dose is often used. Unsuitable strategies are chosen. There is some type of erroneous decision made to reduce the risk of bleeding and that patient is prescribed an antiplatelet therapy, which really has poor efficacy and does not really reduce the risk of bleeding compared to Warfarin. So, oh, let's put them on an aspirin. That'll save them some risk. Not really. They're going to have a GI bleed. Let's choose a low INR target. Well, you're not going to prevent them from having a stroke and you're still going to have a GI bleed, so you're not doing them any favors. Let's use a lower dose of a Doac. It's not going to prevent a stroke and they're still going to bleed. I don't know what dose of Doac to use. They're going to bleed. So I think there's a lot of the wrong dose, the wrong drug is often a problem in treating the elderly. If you look at the clinical trials, you can't compare them side by side, but they have shown a net benefit to the Doacs versus VKA in this patient population. There is a lower risk of bleeding, intracranial bleeding. There's less drug interaction. There is a more favorable outcome for preventing cognitive impairment and there's less progression of CKD. Multi-meta-analysis has also shown time and time again that they are superior to Warfarin and they should be used. The problem is Doacs in the real world do not compare to the use in the clinical trials. We are not using them appropriately and these are the real world trials and showing that very high percentage of the time, up to 24, even in 48% of the time, we are not using these drugs appropriately. We're not using the right dose. We're not using them correctly. So my plea, the take-home points from my talk, is weigh the risks and the benefits. There are times where you cannot use these drugs, but age alone is not a reason to withhold therapy. Use the right medication. Use the right dose. Use Hippocrates. Look it up. Look up what the parameters are that should dictate to you what dose, what drug, and how to modify your regimen as different scenarios arise in your patient care. Thank you for your attention.

anticoagulation

atrial fibrillation

embolic events

CHA2DS2-VASc score

elderly population