Future of Thromboprophylaxis and Final Thoughts

Deepak Bhatt, MD, MPH: In the final few minutes we have we can talk a little bit about what the future holds. We’ve talked a lot about what’s there, what’s available, what’s FDA approved, what is not yet guideline-approved that probably should be. What does the future hold for this field, in terms of things like not just longer duration? I’d love to hear your thoughts on even longer duration beyond what’s labeled and approved right now. Does it need formal study? Are such studies under way? Then just potentially other approaches or agents, either drugs or maybe even devices. What’s going on?

Gregory Piazza, MD, MS: One of the concepts that I already mentioned was this idea that patients are at risk for venous thromboembolism before they’re admitted. I think potentially one of the future avenues for investigation may be prophylaxis, pre-hospitalization in a patient that you think might ultimately end up needing to be hospitalized. You might see a patient in primary care clinic that you’re going to observe over the next couple of days and make a decision about admission or not. That might be a patient that, in a trial, this needs to be studied and proven, but that might be a concept that we start to look at in the next few years.

Deepak Bhatt, MD, MPH: For example, someone with a heart failure exacerbation, you’re trying not to admit them but you’re diuresing them at home.

Gregory Piazza, MD, MS: Maybe they’re going to an advanced center or one of those centers where they’re getting infusions.

Deepak Bhatt, MD, MPH: Sure, shot of IV diuretic once a day. That’s really a great idea for a trial. What other thoughts in terms of what’s new, or could be new, or should be new?

Gary Raskob, PhD: I think for taking what we know now and implementing it, I’ll address that first. I think there’s going to be a lot of ongoing trials. Number one is risk assessment in all hospitalized patients. I think what’s happening or changing is payment models are starting to align with these things in terms of the way healthcare will be paid in the US, with more emphasis on population health and keeping them healthy that fits with preventing events like VTE [venous thromboembolism] and other things after hospital discharge, where the hospital may pay a financial penalty.

I think risk assessment in everybody, select people for appropriate duration prophylaxis because hospitalization is only 3 or 4 days. You still need to give at least somewhere between 6 and 14 days as a minimum, because that’s what the trials that showed benefit were based on. Then who might get 30 days, that’s one thing. I think this is going to move into you have a patient who develops deep vein thrombosis or pulmonary embolism and survives that, where the field is more moving to is a paradigm shift from what we used to do was treat people for 3 months and then say, who needs to go longer and try and get them off anticoagulation because warfarin was so problematic in high risk of bleeding.

This field is going to transition more to extended treatment—or indefinite treatment—will be the default for most people with an established VTE, and then you’ll select who is not safe to continue going forward. The concepts of we have different groups of people for risk of recurrence and so on. The risk of recurrence is sufficiently high in most people that given our very low risk of major and fatal bleeding, we’re going to be defaulting more to extended treatment for most people who develop VTE. It speaks to Mike, but he, as a cardiologist, was surprised about these rate of events at 3, 4, 5 years in patients with VTE. So, in people who develop VTE who are going to see more indefinite, or life, treatment with 10 mg of rivaroxaban or 2.5 mg of apixaban twice a day.

Deepak Bhatt, MD, MPH: That’s great. Any other final thoughts, Mike?

C. Michael Gibson, MS, MD: Sadly I think cardiovascular disease, including venous thrombosis, remains the biggest killer worldwide. 1 in 4 deaths are related to thrombotic disease of some type.

Deepak Bhatt, MD, MPH: That’s a sobering statistic.

C. Michael Gibson, MS, MD: It is a sobering statistic. The sad thing we’ve seen though is the pivot away from population health over to rare diseases. We’ve seen a pivot away from investment in cardiovascular disease at a 20% rate down to 5% to 10%. We’ve neglected population health. We’ve neglected cardiovascular disease, partly because the cost of goods was so high in terms of trials. I think we’re on the precipice of having digital health technologies like what we’re doing in one of the trials with the Apple Watch, where we’ll randomize 180,000 people to give them a watch or no watch. We’re going to do it very inexpensively at 1% of the cost of doing a randomized trial.

Deepak Bhatt, MD, MPH: That’s amazing.

C. Michael Gibson, MS, MD: People will enter. They’ll use an app to get consented. We’ll cut out a lot of the bricks and mortar. We’ll then look at outcomes. We’re going to have a clinical event committee looking at it. We’re going to use claims databases. My hope is that by enabling patients to engage in more trials at a fraction of the cost, we get more shots on goal in the cardiovascular space, get back in there, have a rebirth in cardiovascular research in some of the things like factor XI inhibitors. Well, here we’ve got a population that’s at high risk of bleeding. If we can lower that risk with a factor XI inhibitor, maybe one that’s injected at discharge, and assess it for 1% of the costs the way we used to, I think we can make a lot of progress.

Deepak Bhatt, MD, MPH: Yeah, those are great approaches, and they’re a great class of medicines that’s being evaluated as an antithrombotic. Any other final closing thoughts?

Alex C. Spyropoulos, MD, FACP, FCCP, FRCPC: I think we are entering the era of the pragmatic clinical trial design. One of the things that has really impressed me, because I’ve worked now closely with our informatics department in the last 2 years, is the growth sophistication with informatics to help us reach our goal. I think some of the things that were echoed here was implementation, especially universalization at a systems level of all these processes, using things like electronic discharge alerts, using things like usability testing, so make it easy for the clinicians, and make it within the workflow, and make it so that it’s automatized as much as it can using logic, and using part of the workflow so that they don’t miss a beat. It makes the workflow easier, not harder.

We are hoping to get a grant to conduct a 12,000-patient pragmatic trial using something called Smart On Fire technology, which essentially, if successful, we’re able to universalize, for example, the IMPROVE tool and then make it accessible in any EHR [electronic health records] environment. Make it EHR-agnostic, so use a Smart On Fire version of the IMPROVE tool as a clinical prediction tool, make it access the health informatic exchange environment, make it autopopulate, and then connect it to an order entry. So that it’s all automated, both at admission and at discharge and maybe even post-discharge.

I do think as a last point to what Greg said, data suggests that about 5% to 10% of patients with chronic medical illness may benefit from long-term primary prevention. We just have to get a better feel of who these patients are, and now that we have safer options, I think that’s a great group to maybe think about for prolonged primary prevention. I’m thinking of the elderly nursing home patients, patients in long-term care facilities with chronic cardiopulmonary disease. That’s a great group of patients.

Deepak Bhatt, MD, MPH: It is.

Alex C. Spyropoulos, MD, FACP, FCCP, FRCPC: It’s a pretty large denominator.

Deepak Bhatt, MD, MPH: Yeah, that really is. Well, look, it’s been a terrific discussion. It’s been fun, it’s been lively. Hopefully for our audience it’s also been educational. On behalf of our panel, we thank you for joining us, and we hope you found this Peer Exchange discussion to be useful and informative. I certainly did. Thank you for those of you at home for joining.

Transcript edited for clarity.