Extended Thromboprophylaxis in Medically Ill Patients - Episode 11

Reducing the Burden of VTE

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Alex C. Spyropoulos, MD, FACP, FCCP, FRCPC: In my view, the guidelines on the topic really need to be updated.

Deepak Bhatt, MD, MPH: I think we can all agree on that.

Alex C. Spyropoulos, MD, FACP, FCCP, FRCPC: And individualized risk adapted approach, I think, is on the order of business. Because the way the guidelines read right now, 100% of patients should not get any post-hospital discharge prophylaxis.

Deepak Bhatt, MD, MPH: And just for the sake of the audience, I’m glad you brought up guidelines. It’s important to always discuss them. Which guidelines are you referencing?

Gregory Piazza, MD, MS: The ASH Clinical Practice Guidelines.

Alex C. Spyropoulos, MD, FACP, FCCP, FRCPC: These are the American Society of Hematology Guidelines in 2018, so they’re only a year old.

Deepak Bhatt, MD, MPH: Yeah. Well, it’s tough to keep guidelines up to date these days. The data is just coming in, in all aspects of cardiovascular medicine, at a furious pace.

Gary Raskob, PhD: Just to finish this piece.

Deepak Bhatt, MD, MPH: Finish it.

Gary Raskob, PhD: I think for me the most important point is, to the point of the guidelines, is the paradigm change. And I think the benefit patients are going to get and the impact we’re going to have on population health in reducing the burden of VTE is going to be achieved by prophylaxing patients who historically weren’t given prophylaxis, and we’ve talked about how to select them. And the choice between betrixaban and rivaroxaban is going to be very marginal in terms of the difference that it’s going to make. So what’s available to the doctor, what they’re comfortable with, if they use rivaroxaban for other things, they’re very comfortable with the 10 mg of approved dose that’s on many formularies right now. If it’s available to you I think it’s much more important to be changing towards identifying those patients that should get this prophylaxis and giving it, and the differences between the drugs are more academic at this point.

Deepak Bhatt, MD, MPH: Absolutely. Like most debates, really the truth is right in the middle, as you guys all agree.

C. Michael Gibson, MS, MD: Good to know one drug really well.

Gregory Piazza, MD, MS: That’s what I was going to say. Get comfortable with something for this indication, and then the patient wins.

Deepak Bhatt, MD, MPH: No, that’s really good advice. Though it gets tricky again because what if you are most used to apixaban, the best for AFib [atrial fibrillation], I think that’s the most popular NOAC [novel oral anticoagulant] for atrial fibrillation at this point.

C. Michael Gibson, MS, MD: It may be the most popular, but, again, I would emphasize a lot of that’s driven by bleeding, and I’d also emphasize that the criteria for bleeding was different in, I’d say the ROCKET trial and the apixaban trials. In the RIVA trials you could drift down slowly in your hemoglobin and get called a major bleed. With the apixaban experience, it had to be a fairly quick bleed. And, when you analyze the apixaban data the same way you do the RIVA data, you see no difference in the bleeding. I think we have to really be careful when we look at these cross-trial comparisons and be very thoughtful about it.

Deepak Bhatt, MD, MPH: That’s really great advice in general. What about warfarin, any role here at all?

Gregory Piazza, MD, MS: It is cheap. It’s familiar.

Deepak Bhatt, MD, MPH: They always ask about it.

Gregory Piazza, MD, MS: Yeah. I think the problem with warfarin is the bleeding that we mentioned, we’re all worried about the bleeding that patients might experience on it. They’re going to be on it, even for extended duration, for a limited amount of time, and there’s a period of time where we’re trying to get that INR [international normalized ratio] into the target range. And there are two issues about that. We want them protected right away, and we don’t have time to wait. A lot of that risk, as Alex talked about, is in those few days after they’re discharged, even the month after they’re discharged. And the other issue is they can be supratherapeutic and have a risk for bleeding which is not what we want for our patients either. I don’t think, there aren’t good data to support it and the DOACs basically make the conversation rhetorical.

Deepak Bhatt, MD, MPH: I think you’re quite right. That summarizes it very well. What about a patient who comes in, let’s say, they’ve had an ischemic cardiomyopathy. They’re in with heart failure. They got a stent two-and-a-half months ago, they’re on aspirin and clopidogrel, let’s say. What exactly do we do with that patient, should we add on this extended duration, should we not do it? How do we treat those patients? Does anyone have any opinion, or data, or strong feeling?

Alex C. Spyropoulos, MD, FACP, FCCP, FRCPC: Well, we know that dual antiplatelet therapy is actually one of those five key high bleeding-risk criteria that we saw in MAGELLAN and I believe also in . So we do have some data suggest that in addition to even a low dose anticoagulant may predispose the patient for bleed risk. I guess the question is, and talking to my cardiology colleagues, is there a way we can remove one of the antiplatelet agents as the first order of business? And if the answer is no, then again, in my point of view, that probably would be a patient that we would consider mechanical methods of prophylaxis.

Deepak Bhatt, MD, MPH: Sure.

Gary Raskob, PhD: So the dual antiplatelet patients were not enrolled in the MARINER study, for example, because of the bleeding risk and so on. So I think you need to manage first what their cardiac stuff is and then think. So, for the in-hospital phase, you can add mechanical prophylaxis without any added risk of bleeding.

Deepak Bhatt, MD, MPH: What about if they’re on aspirin monotherapy say because they had an MI [myocardial infarction] four years ago?

Gary Raskob, PhD: Those patients were allowed.

Alex C. Spyropoulos, MD, FACP, FCCP, FRCPC: As a matter of fact, 50% of patients in MARINER were on a single antiplatelet therapy, mostly aspirin.

C. Michael Gibson, MS, MD: Yeah, we had that, too.

Deepak Bhatt, MD, MPH: There’s talk about warfarin made something else pop into my mind. I’m going back a little bit and talk about inpatients and heparin and I mentioned or asked before about outpatient use as well of low molecular weight heparin. What are your thoughts about what’s going on with the heparin shortage? I know at our hospital, it’s been a bit of an issue.

Gregory Piazza, MD, MS: Yes. I was on that committee.

Deepak Bhatt, MD, MPH: Oh, so you’re to blame for the heparin shortage.

Gregory Piazza, MD, MS: No, no, I didn’t contaminate the porcine population. No, it’s been a major issue because we’ve had to come up with a set of guidelines of what to substitute. And I think this is an opportune time for us to rethink why we’re using heparin at all for prophylaxis. Unfractionated heparin has not been shown in meta-analysis to be as good as enoxaparin. And we have the direct oral anticoagulants that seem to be a great option. This might be a very opportune time to work in what we probably should be doing anyway, which is switching to oral anticoagulants that have great safety and great efficacy.

Alex C. Spyropoulos, MD, FACP, FCCP, FRCPC: To tell an 80-year-old, well, get three injections of heparin in your belly every day for four or five days versus a pill, that’s not a difficult choice.

Deepak Bhatt, MD, MPH: It has at least, maybe the heparin shortage is changing it, but until then at least it’s still a common practice in many hospitals.

Transcript edited for clarity.