Low- vs High-Dose Anticoagulation Therapy and Risk-Stratifying Patients

In this podcast, Anne Rose, PharmD, talks about her session at the Anticoagulation Forum 2021, during which she highlighted the factors associated with increased risk of recurrent VTE, appropriate duration of anticoagulation for VTE depending on risk/benefit analysis, and extended anticoagulation.

Additional Resource:

• Rajasekhar A, Rose A. High dose vs low dose: duration of therapy debate. Talk presented at: Anticoagulation Forum 2021; October 28-30, 2021;Virtual. https://acforum.org/virtual/index.php?page=presentation&session_id=9&presentation_id=49

Anne Rose, PharmD, is the pharmacy manager at University of Wisconsin Health in Wisconsin.

TRANSCRIPT:

Amanda Balbi: Hello and welcome to another installment of Podcasts360, your go-to resource for medical news and clinical updates. I’m your moderator Amanda Balbi with Consultant360. 

Our guest today is Anne Rose, who is a PharmD at the University of Wisconsin and UWHealth. She will be speaking with us about her recent session at the Anticoagulation Forum, during which she discussed high-dose vs low-dose anticoagulation therapy and the debate around duration of therapy.

Thank you for joining us today, Anne. To begin, can you give us a brief overview of your session and any of the research that you presented?

Anne Rose: The overview of our session is really to focus on the duration of anticoagulation therapy in patients who are diagnosed with VTE (venous thromboembolism), so looking at the patients who are appropriate for the usual 3 to 6 months, who to consider for extended anticoagulation therapies.

Then we dive into some of the low-dose options for the direct oral anticoagulants, or the DOAC class, looking at some of that data to see when we would maybe want to consider utilizing more of the prophylactic dose for that extended anticoagulant therapy.

Amanda Balbi: So, let's dig in a little bit. Let's talk more about the patient groups, the populations who qualify for anticoagulation therapy, and let's take it through low-dose to high-dose.

Anne Rose: Our presentation is split into 2 groupings. We have the groups of patients where their VTE is caused by a particular agent, commonly known as the provoked group. We go down the route of looking at the causative factor, is it something that's more of a major vs a minor risk factor?

We talk a lot about a risk-benefit discussion, especially when patients finish that initial treatment stage, and who then to consider for extended therapy. Again, looking at patients who have provoked VTE by one of these more minor risk factors or who maybe are at a lower risk for overall bleeding from anticoagulation.

I think the theme of our presentation is to try to keep patients on anticoagulation therapy as long as possible. We know that when patients come off of anticoagulation therapy, there is potential for the risk to have another event. So, it's really about finding those patients where it is safest from that risk-benefit standpoint to not do extended therapy, and for those patients who we are considering for extended therapy, then who is that category of potentially looking at the lower dose.

For the unprovoked category, which typically are those patients who have VTE but we don't really have a good factor as to why they got it, and then really again going down that risk-benefit of who really are the highest-risk patients. Those are the groups that we're going to be keeping on full-dose anticoagulation extended vs those patients who have been studied in some of these newer DOAC studies, where we can maybe go down and do more of the prophylactic dosing.

Amanda Balbi: Interesting. Can you talk a little bit about risk stratifying those patients? How do you determine those patient populations?

Anne Rose: For the provoked group, a lot of it is looking at the causative factor. If it's a major risk factor like, let's say surgery for example, we know that those patients typically don't have a huge risk for recurrence. So, those are the really clear-cut patients that we can say, “Yes, we can treat for that 3 months,” and feel pretty confident that they can come off of anticoagulation.

It's the group that have a minor risk factor that caused it or a nonsurgical trigger where we just don't have as good of information. We know there is a risk for recurrence, and that's when you start looking at “What is their overall bleeding risk? Does the risk for bleeding then outweigh extending these patients?”

There are some risk-prediction tools that we cover as well, like looking at “Is your patient female or male? Do they have any other type of underlying thrombophilia?” That might weigh into that as well. “Is the factor that caused the VTE still present, or is it gone?”

We would walk through a couple of those examples to really hone in on how you do those risk-benefit scenarios and whether to stop your patient on anticoagulation vs continue. A lot of it really is looking at the bleeding risk for the patient to determine whether or not it's worth it, in a sense. Are we getting enough benefit from preventing VTW without tipping the scale on the side of bleeding?

And then those patients who have unprovoked VTE, again looking at the different extension trials. So, we talked about for, say, the cancer patient population and the data that's out there from treating beyond 12 months, depending whether cancer is still present or not.

We also looked at the lack of data, too, that’s out there for using these prophylactic doses, and really determining you know when to consider those patients. I think that's an area that we still need more information on. Who are those patients who we could trial these lower doses in that extended anticoagulation phase? We have some initial studies, but again they typically have only followed patients for about a year, so we still don't know what the long-term risks or benefits from doing that. 

That's an area that we talked about as a still needing some more information before putting everybody on a prophylactic dose after that first year of a full-dose anticoagulation.

Amanda Balbi: Great. So, what would you say—I know you started talking about this—is the next step for research? What else needs to be extrapolated?

Anne Rose: I think that's really the biggest area—looking at the extended phase. We have a good sense of knowing that patients should at least be treated full-dose anticoagulation for the first 3 to 6 months. I think that's really not too controversial. So, we know that's at least our baseline. We start there, and then really everything beyond that is where we're not 100% sure.

We obviously always lean towards continuing, because we know that that’s really going to help prevent recurrence. But I think in these situations where you have patients with different risk factors on top of their VTE—they have cancer, they have thrombophilia, they are a warfarin vs a DOAC patient, they have different levels of bleeding risk factor. It's those patients we're just not sure if we’re doing more harm than good from these extended treatments. 

Then again, of course, can we utilize more low-dose options? Then, I think the other area, too, is patients who are at a high risk of bleeding and maybe they did bleed or had an event. If you're stopping anticoagulation for that bleeding event, what does it look like from a restarting standpoint? Is it beneficial to restart in certain patient populations, again, to make sure they're not getting recurrent VTE events.

I think that's still an area where many of us clinicians are a little bit hesitant to say we know for sure the answer of how to treat those patients.

Amanda Balbi: What would you say are your overall clinical take-home messages from your session? And how would those take-homes be implemented in practice?

Anne Rose: Our take-home message really is 3 points. One is, do you have a cause for what causes VTE? So looking at whether we know if it was from a certain risk factor or not.

I think our biggest take-home point is this risk-benefit discussion. We pretty much agree that this treatment timeframe of 3 to 6 months is really where we should be striving for every patient. Then those risk-benefit discussions come in with the patient afterwards and really tying in the patient to that, too. We very frequently look at, “Oh, here are their risk factors for clotting. Here are the risk factors for bleeding.” 

But we also have really stressed in this presentation to make sure that you're getting your patient’s preference, too, and that the patients have a voice in how they want the direction of their care to go. Having that discussion on whether it is worth it to do extended therapy vs ending after that initial treatment time. The next step doesn't need to be full dose in that extended realm, or we can do a prophylactic dose.

I think the other part, too, is just a regular reassessment. If at that initial conversation your patient decides to continue, make sure that we're not just putting those patients on anticoagulation and then never having those discussions again. Make sure that—whether its annual or biannual, however 
frequently you're seeing the patient—to continue to have those risk reassessments.

We know patients’ bleeding risks will change over time, depending on their age or other factors that they have. Same thing with VTE recurrence. Those things can change over time, too, so just making sure that we are continually looking at that and having those risk reassessments.

Amanda Balbi: I like also that you brought up the multidisciplinary team but also including the patient in the decision-making process. That's one of the themes that I've heard from other Forum speakers.

Anne Rose: I think that's really been kind of a hot topic in health care lately—making sure that the patient’s voice is heard. I know from a pharmacist’s standpoint, we're always taught that you can prescribe whatever you want for the patient, but if they don't actively take it and participate, then you're obviously not going to see the benefit of what you're trying to treat or help along the way. So, having the patient buy-in is huge, even from a compliance and adherence standpoint.

Amanda Balbi: Thank you for your time today, and thank you for answering my questions.

Anne Rose: Thanks so much for reaching out.