My name's Gregory Piazza. I'm one of the vascular medicine cardiologists at Brigham and Women's Hospital in Boston, Massachusetts. And I'm going to be talking about the HI-PRO trial focused on prevention of recurrent venous thromboembolism in patients who've had a provoked venous thromboembolic event.

What is the importance of HI-PRO?

The HI-PRO trial really was born out of this recognition that for quite a while we have dichotomised patients with venous thromboembolism into either provoked or unprovoked. Unprovoked patients typically get long-term anticoagulation—no specific end date, they just keep going. Provoked venous thromboembolic patients who have an event in the setting of some kind of a trigger typically are treated for about three months and then stop.

But there's this whole population of patients who've had a provoked event and have enduring risk and no one really knows how long to anticoagulate those patients. So that really formed the context for HI-PRO.

Could you tell us about the study design and patient population?

The study design of HI-PRO really focused on a single-centre but randomised controlled trial. And we identified a population of patients that were, as I had mentioned, sort of underserved by the current literature.

Patients who had venous thromboembolism in the setting of a provoking factor, who had some sort of enduring risk. It could be obesity, it could be cardiovascular disease, could be inflammatory disease. They had to have received at least three months of anticoagulation and then they were enrolled into the study, and we randomized them to receive either apixaban 2.5mg twice daily, which is a direct oral anticoagulant, or a matched placebo.

What were the key findings from the trial?

The key findings of HI-PRO really were: one, that we identified that patients with provoked venous thromboembolism and enduring risk factors do have a high risk of VT recurrence. Low intensity apixaban with 2.5mg twice daily was effective and reduced the risk of recurrent symptomatic venous thromboembolism by 87%. And it did that without increasing major bleeding as defined by the ISTH. Now, there was a numeric increase in the rate of clinically relevant non-major bleeding, but that didn't really reach statistical significance.

What is the potential clinical impact of these findings?

So the clinical impact of HI-PRO is: one, that there's this new population of patients with provoked venous thromboembolism who have enduring risk that actually have a high enough risk of recurrence that we should talk to our patients about continuing anticoagulation, and that low intensity apixaban 2.5mg twice daily is effective for reducing that risk of recurrence with a low risk of bleeding, especially major bleeding.

How should these findings impact future guideline recommendations?

For the evidence-based clinical practice guidelines, they up until now have really been limited to unprovoked venous thromboembolism patients where they universally recommend long-term anticoagulation, and then patients with provoked venous thromboembolism where they typically have recommended short-term anticoagulation.

Now guidelines will have to incorporate both observational data which for quite some time now has suggested there's a hazard to patients with provoked venous thromboembolism. It's not a negligible risk of recurrence, and with HI-PRO actually showing that the risk of recurrence can approach 10%, guidelines are now going to have to recommend likely a greater emphasis on shared decision making with patients and talking about extending anticoagulation if there's some enduring risk.

What is your key take-home message for clinicians?

The key take-home messages of the HI-PRO trial are: one, that there is this population of patients with provoked venous thromboembolism and enduring risk who have a high enough risk of recurrence that we do need to talk to them about extending anticoagulation, and that essentially, low intensity apixaban is a fine way of protecting those patients with good efficacy and a low risk of major bleeding.

What are the next steps?

I think the next steps after HI-PRO will be to continue to refine our understanding of these populations of risk. In HI-PRO, we took patients who had enduring risk factors that could be identified, but there are going to be patients that probably were left out of the trial that have a high enough risk.

So we could consider doing future trials with AI informed risk scores, with polygenic risk tools, and even some biomarkers that might identify patients that might slip through the cracks of a clinical assessment but have a high enough risk to warrant receiving long-term anticoagulation.