Behnood Bikdeli, MD, MS, is a physician at Mass General Brigham and assistant professor of medicine at Harvard University.

Behnood Bikdeli, MD, MS

Long-term treatment with apixaban reduces 

 recurrence, but stopping active treatment negates this benefit, according to a long-term follow-up to the HI-PRO trial.

Long-Term Apixaban Treatment Improves VTE Recurrence Risk, Benefit Fades After Discontinuation

American Heart Association (AHA) Scientific Sessions 2026

 in Chicago, Illinois, by Behnood Bikdeli, MD, MS, a physician at Mass General Brigham and assistant professor of medicine at Harvard University.

“The question of apixaban’s effectiveness has largely been settled, in my opinion,” Bikdeli told 

 in an exclusive interview. “The real question that we tried to answer in the extension study was what happens after they 

 this randomized blinded regimen compared with placebo.”

HI-PRO was a randomized controlled trial evaluating extended-duration low-intensity apixaban versus placebo to prevent recurrence of provoked VTE in high-risk patients. Patients were eligible for inclusion if they had objectively confirmed provoked deep-vein thrombosis (DVT) and/or pulmonary embolism (PE), had been treated for ≥3 months with standard anticoagulant therapy, and had not suffered symptomatic recurrence during prior therapy, among other criteria. Patients with active cancer within 5 years, contraindications to antithrombotic or antiplatelet therapy, or active severe hepatobiliary disease, among other criteria, were excluded.

Eligible patients were randomly assigned to receive either apixaban 2.5 mg orally twice daily for 12 months or matching placebo. The study involved 2 primary endpoints, which were the frequency of symptomatic recurrent VTE and of major bleeding in 12 months. Secondary endpoints included the frequency of a composite of cardiovascular mortality, nonfatal myocardial infarction, stroke, or systemic embolism, critical ischemia, or coronary or peripheral ischemia requiring revascularization, among others.

A total of 600 patients were enrolled in the initial HI-PRO study, among whom mean age was 59.5 years and 57% were female. The most common provoking factors for VTE were surgery (33.5%), immobility (31.3%), trauma (19.2%), and acute medical illness (18.3%). The most common enduring risk factors included chronic inflammatory or autoimmune disorder (52.2%), a body mass index ≥30 (48.2%), and atherosclerotic cardiovascular disease (29.3%).

Symptomatic recurrent VTE occurred in 4 of the 300 patients in the apixaban group compared to 30 of the 300 patients in the placebo group (HR, 0.13; 95% CI, 0.04 to 0.36; 

 <.001). Major bleeding occurred in only 1 patient in the apixaban group and none in the placebo group, while clinically relevant nonmajor bleeding was observed in 14 of 294 patients in the apixaban arm and 5 of 294 in the placebo arm (HR, 2.68%; 95% CI, 0.96 to 7.43; 

The present 24-month follow-up to HI-PRO was composed of 12 months of randomized treatment and a 12-month post-treatment extension. During this period, anticoagulation was determined by treating clinicians blinded to the original trial. Bikdeli and colleagues established a primary effectiveness outcome of symptomatic recurrent VTE, while the principal safety outcome was major bleeding.

At 24 months, Bikdeli and colleagues found that recurrent VTE occurred in 5.8% of patients receiving apixaban and 12.9% assigned to placebo (absolute difference, -7.1%; adjusted risk ratio [aRR], 0.41; 95% CI, 0.22 to 0.64; 

 = .001), with nonproportional hazards over time. Major bleeding was noted in 2% of patients on apixaban versus 0.7% on placebo (absolute difference, 1.3%; aRR, 3.07; 

 = .88). Over the second 12 months, recurrent VTE did not differ significantly between groups (aRR, 1.23; 95% CI, 0.54-3.51; 

Ultimately, Bikdeli and colleagues determined that 1-year treatment with low-intensity apixaban substantially reduces 2-year risk of recurrence. However, the loss of benefit during the period after stopping regular treatment, they noted, highlights the importance of long-term risk management in this population.

“The main trial showed a large effectiveness signal. Now, the extension study is suggesting that the effectiveness goes away if you do not continue the treatment, which makes sense in retrospect for a medication that is short-acting,” Bikdeli said. “I think the bottom line should be continued shared decision-making for patients who have provoked venous thromboembolic disease and enduring risk factors.”

Editors’ Note: Bikdeli reports no relevant disclosures.

Bikdeli B, Rashedi S, Pfeferman M, et al. Apixaban vs Placebo to Prevent Recurrences in Provoked Venous Thromboembolism With Enduring Risk Factors: One-Year Extension Results From the HI-PRO Trial. Presented at the American Heart Association (AHA) Scientific Sessions 2026, Chicago, IL. November 6-9, 2026.

Brigham and Women’s Hospital. Extended-Duration Low-Intensity Apixaban to Prevent Recurrence in High-Risk Patients With Provoked Venous Thromboembolism (HI-PRO). ClinicalTrials.gov Identifier: NCT04168203. Updated November 14, 2025. Accessed November 8, 2026. 

https://clinicaltrials.gov/study/NCT04168203

Piazza G, Bikdeli B, Pandey AK, et al. Apixaban for Extended Treatment of Provoked Venous Thromboembolism. 

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Behnood Bikdeli, MD, MS, discusses his long-term follow-up to the HI-PRO study, which noted apixaban’s lasting effects on venous thromboembolism.

Behnood Bikdeli, MD, MS

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