Selecting an Anticoagulant in NVAF

Peter Salgo, MD; Ralph J. Riello III, PharmD, BCPS; Gary M. Besinque, PharmD, FCSHP; Jaime E. Murillo, MD; and Juvairiya Pulicharam, MD, compare the use of warfarin with a novel oral anticoagulant as appropriate therapy for patients with nonvalvular atrial fibrillation.

Peter Salgo, MD: Now let’s talk about these novel oral anticoagulants versus warfarin. Which one works better?

Ralph J. Riello III, PharmD, BCPS: That’s a very leading question. These are all evidence-based therapies that have been widely studied in nonvalvular atrial fibrillation. This drug class is expanding. I’d actually challenge that these novel anticoagulants aren’t very novel anymore. Dabigatran came out about 10 years ago and, of course, warfarin, in 1950. With regards to preventing stroke and systemic embolism, they’re basically apples to apples. It’s really saving on the bleeding side of things. That’s where you derive a lot of benefit from using the direct oral anticoagulants.

Peter Salgo, MD: Explain that. Why?

Ralph J. Riello III, PharmD, BCPS: The kinds of bleeds that they tend to cause are cut in half. You do pay a little bit of expense on the gastrointestinal bleeding side, but in terms of fatal and intracranial bleeds, it’s about half the risk with this drug class.

Peter Salgo, MD: The bleeding profile of the novel agents is more on the gastrointestinal side, and the bleeding profile of Coumadin, or warfarin, tends to be a little higher intracranially?

Ralph J. Riello III, PharmD, BCPS: Yes.

Peter Salgo, MD: Given my choice—gastrointestinal bleed or a stroke from hemorrhage—I know what I’d pick.

Ralph J. Riello III, PharmD, BCPS: That’s an easy decision.

Peter Salgo, MD: Do we know why that risk stratification is? Why is one more intracranial, and why is one more gastrointestinal?

Ralph J. Riello III, PharmD, BCPS: We’ll talk about warfarin’s mechanism, but we know it impairs vitamin K—dependent clotting factors II, VII, IX, and X. Factor VII really gets the coagulation cascade started by binding to tissue factor. We’ve evolved to express a lot of tissue factor in our brain to quickly stop a bleed there. Because warfarin is depleting our basic way to form factor VII, it can’t make that connection with tissue factor in the brain to prevent or stop an intracranial hemorrhage once it happens.

Peter Salgo, MD: There’s a real biochemical reason for this. Again, if you have a gastrointestinal bleed, I’ll transfuse you. We’ll fix it. If you’re having an intracranial bleed, which is why I got on your case earlier, I’m not sure. I could reverse it, but by then, you’ve got intracranial pressure and all sorts of trouble, right? I just assume not to have one of those.

Gary M. Besinque, PharmD, FCSHP: Absolutely.

Peter Salgo, MD: We like the risk stratification, in terms of where the bleed is with novel agents versus warfarin. Is that fair?

Jaime E. Murillo, MD: Yes.

Peter Salgo, MD: Still, people are being put on warfarin. Is that fair? Is it true that warfarin is still the go-to drug for most primary care physicians?

Jaime E. Murillo, MD: I think there’s a difference in terms of practice, and it comes back to your point of education. There are areas in which a lot of practitioners prescribe warfarin. I would not use it if I had the choice, but that’s a conversation to have with the patient. You have to start with that. You have to tell a patient, “These are the choices,” and, “These are the pros and cons.” A big one is cost. Some patients will say, “I’m going to stick to warfarin because that’s the only thing that I can afford.” You can tell them about the cost of a gastrointestinal bleed, or the risk of it, and so on, but it’s still used. Should it be the go-to drug? I don’t think so.

Peter Salgo, MD: Sometimes drugs are used because they’re used, because they’re used, because they’re used.

Juvairiya Pulicharam, MD: I agree that patients, if given a choice and educated on it, would choose something that’s easier. I think the primary care physicians, when their patients are on warfarin, kind of feel that the patients are more monitored.

Gary M. Besinque, PharmD, FCSHP: That’s right.

Juvairiya Pulicharam, MD: It’s really not knowing the difference and being comfortable with it.

Gary M. Besinque, PharmD, FCSHP: They’re happy to get the INR checked. You want to know that your patient is taking it, and you want to know that you’re within the therapeutic range. You don’t have the benefit of lab values for the novel agents.

Peter Salgo, MD: The implication of knowing the INR as an indicator, or whether or not the warfarin is being taken, and whether it’s clinically effective, is that somebody’s got to come back. You’ve got to draw the blood and get the INR. That’s a major burden, isn’t it? It costs money, and you’ve got to have a group of people doing this.

Juvairiya Pulicharam, MD: That’s an indirect cost.

Peter Salgo, MD: It’s a real cost. If I want a drug, I don’t think I’d want to come back and get stuck every couple of weeks. How often do you bring people back anyway, in the real world?

Jaime E. Murillo, MD: You have to start early and frequently. You’re going to start the medication. If you’re being treated as an outpatient, you have to come back in 3 days to get the first one and then every week until you get to certain levels. And then for the week it is off, you have to restart the clock and start coming back more frequently. Then it’s once a month and so on. There are monitoring devices for use at home. Interestingly, you’re now talking about INR, which is more of a psychological issue. When you talk to patients about the NOACs, they say, “How do I know if it’s working?” I say, “How do you know whether your antibiotic or aspirin or other medications are working? You’re not checking them.” It’s just a matter of getting into their brain and explaining that.

Peter Salgo, MD: Warfarin offers you the anticoagulation meter. Everyone likes it. It’s like your gas gauge. You like to know when you’re running out of gas. But you don’t need it, I gather?

Ralph J. Riello III, PharmD, BCPS: No, you don’t. There is even a problem with warfarin and INR in patients who were managed well. In the studies, where patients were closely followed in multiple visits, about a third of the time, they were out of range.

Peter Salgo, MD: High or low?

Ralph J. Riello III, PharmD, BCPS: Either/or.

Peter Salgo, MD: Really? What’s worse, overanticoagulation or underanticoagulation?

Jaime E. Murillo, MD: There you go. That’s a good question.

Gary M. Besinque, PharmD, FCSHP: I would go with underanticoagulation.

Ralph J. Riello III, PharmD, BCPS: Yes.

Gary M. Besinque, PharmD, FCSHP: Like you said, the consequences of a cardioembolic stroke are a lot worse than losing some blood.

Peter Salgo, MD: I once saw a closed claims’ analysis of warfarin, and it seemed to me that underanticoagulation was far worse. Again, we can fix the gastrointestinal bleed. If you’re underanticoagulated, you’re now at risk for all the things in which you’re giving this dangerous drug to prevent. So, why give the drug in the first place? Give it, give enough of it, and make sure that the INR is therapeutic, yes?

Ralph J. Riello III, PharmD, BCPS: Yes.

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