NOACs in the Anticoagulation Space - Episode 5
Manesh Patel, MD: I don’t want to be too negative. I think it’s important that we have made progress. I’m just thinking about how we increase better use. Sean, what do you think about that?
Sean D. Pokorney, MD: I guess my concern is that the transition from my perspective is actually relatively rapid, as Dr Califf was mentioning, transitioning to the NOACs [new oral anticoagulants]. The problem has been there hasn’t been that increasing trajectory of overall use of anticoagulation in these patients. I think the guidelines are pretty clear on this as well when we talk about the guidelines and the importance of shared decision making and engaging patients.
We’ve done some studies with qualitative interviewing within the Duke University Health System looking in primary care practices and geriatrics practices. There have been several other studies that have shown this too. There’s still a fundamental disconnect with the way patients see the world and the way providers see the world. That’s 1 of the things we really need to work to overcome. The number of bleeds a patient is willing to tolerate to prevent a stroke is much higher than the number of bleeds a provider is willing to tolerate.
Christopher Granger, MD: I love this study, Sean. I oversimplify it a little, but basically the study showed when you take a population of patients who are not on an anticoagulant for atrial fibrillation [AFib], and you ask the providers why aren’t they on it, and the provider says because the patient refused; they didn’t want the high risk. You go to the exact same patient and get a completely different answer. That’s because it wasn’t described to them that the benefit clearly outweighed the risk.
Bernard J. Gersh, MBChb, DPhil, MACC: In fact, there was a questionnaire, a survey carried out in Canada. Physicians were frightened of bleeding because we cause bleeding. Patients were frightened of stroke.
Manesh Patel, MD: Yes.
Bernard J. Gersh, MBChb, DPhil, MACC: I think underutilization is the fault of physicians, not patients.
Manesh Patel, MD: Certainly I think for some of the data you’re prescribing, they numerically ask patients, how many GI [gastrointestinal] bleeds? How many bleeds require hospitalization? How many of these falls would you take with a bleed that might get you to the hospital? They’re in the hundreds in their minds, and we see 1 and feel very bad about it, because of course we’re trained to do no harm and want to make decisions. But involving them would help.
Robert M. Califf, MD, MACC: I still love the phrase. It shouldn’t be “Do no harm.” It should be, “On average, do more good than harm.” Because everything we do that causes good carries some risk.
Manesh Patel, MD: Of course.
Sean D. Pokorney, MD: I think this is where it’s interesting to engage our neurology colleagues, because we see the bleeding episodes that patients have.
Manesh Patel, MD: They see the strokes.
Sean D. Pokorney, MD: They see the strokes. When you talk to the neurologists, they really highlight what a huge issue it is in these patients and how life changing it is. We know that in AFib-related strokes, almost 25% of people die within 30 days. They have much higher morbidity relative to non-AFib-related strokes. These are large, disabling strokes.
Manesh Patel, MD: Certainly bleeds in the brain are some of those most disabling, effective things we can see. One of the hazards and risks we can think about together is probably that these therapies made a big difference. I’ll end our thought about how we got from 2010 to 2020 and then get into how we do better by saying, what I’ve heard from you all obviously is not to overvalue any effect of aspirin in atrial fibrillation stroke prevention. I think we would all agree that that therapy is not making much difference to patients with atrial fibrillation.
Bernard J. Gersh, MBChb, DPhil, MACC: Except causing some harm.
Manesh Patel, MD: Except causing some harm. On average, you’re not going to be able to do more good than harm if you’re giving an AFib patient at least aspirin most of the time unless there’s some other thing you’re trying to treat. Second, maybe the adoption has gone faster than we think, but these drugs met a high bar and have evolved pretty quickly. We can talk about the separate NOACs in a second. And this is despite different mechanisms of action. Dabigatran Etexilate with a direct thrombin versus the factor Xa, which edoxaban, apixaban, and rivaroxaban certainly have targeted. And they’ve shown again similar efficacy against warfarin when we think about the place the world was in.
Christopher Granger, MD: One other really important thing about warfarin and intracranial hemorrhage—and we’ve seen this in the trials where we have robust data sets—is that if somebody has an intracranial hemorrhage on warfarin, 80% of the time their INR [international normalized ratio] is in the target range or not above 3. This perception, that somebody on warfarin with an INR below 3 is not at risk, is a fallacy.
Manesh Patel, MD: Yeah. In the trials, in fact, we demonstrated that a significant proportion of the patients who were having the ICHs in the trials, their last known INR—we didn’t always get the INR right when they presented—was within range. But of course that’s something we did.
Robert M. Califf, MD, MACC: One thing I worry about a lot is how do we get the world to understand the difference between things that are really empirically proven with really good data and high-quality studies versus—I don’t know what to call it—all the other stuff that people believe that may or may not be true, including doctors and health systems. In this case, there are hundreds of thousands of people now in randomized trials with good data collection, oversight in questioning by many people. This is 1 area where you really ought to be able to put the post down and say this is proved stuff. It’s not just somebody’s opinion.
Bernard J. Gersh, MBChb, DPhil, MACC: It is interesting sometimes to look at the differences in guidelines. The European Society of Cardiology guidelines for some time have said that aspirin is a class III indication, antiplatelet agents for atrial fibrillation. In the ACC [American College of Cardiology]/AHA [ American Heart Association] guidelines, the most recent iteration took that up. Until recently it said that if you are a CHA2DS2-VASc of 1, you’re at increased risk, even if slightly—you could use aspirin, or an anticoagulant, or nothing, which really left it up in the air. It’s only now that I think our guidelines have really looked at the evidence that’s been taken up by other guidelines and said do not use aspirin.
Manesh Patel, MD: That’s absolutely powerful. Rob, to your point, I sometimes put it this way. Let’s do the counterfactual. What if we have 79,000 or 80,000 patients randomized in high-quality 4 trials to show that these agents are better than warfarin? What if I did it the other way: warfarin is clearly better than placebo in 6000 patients, and that’s how we got to now. If I had 79,000 patients, and the pricing and use of these drugs had had 5 years. And then I came to you with warfarin and said, “Here’s what the drug looks like. Here’s what the efficacy is. This is how you have to treat patients with it.” Would you be using it in anyone?
Transcript edited for clarity.