The HI-PRO trial has demonstrated that extended treatment with low-dose apixaban significantly reduces venous thromboembolism (VTE) recurrence in patients with provoked VTE and enduring risk factors, offering new evidence for prolonged anticoagulation in select high-risk populations. The findings were presented at ESC Congress 2025 and simultaneously published in the New England Journal of Medicine.
Trial Design and Patient Population
The double-blind, randomized controlled HI-PRO trial, conducted at Brigham and Women's Hospital, enrolled 600 patients who had experienced deep vein thrombosis (DVT) or pulmonary embolism (PE) following a major provoking factor such as surgery or trauma. All participants had completed at least three months of standard-dose anticoagulation and possessed at least one enduring risk factor.
The study population had a mean age of 59.5 years, with 57% being female. The most common provoking factors included surgery (33.5%), immobility (31.3%), trauma (19.2%), and acute medical illness (18.3%). Enduring risk factors were predominantly chronic inflammatory disorder (52.2%), body mass index ≥30 kg/m² (48.2%), atherosclerotic cardiovascular disease (29.3%), and chronic lung disease (22.3%).
Significant Reduction in VTE Recurrence
Patients were randomized 1:1 to receive either apixaban 2.5 mg twice daily or placebo for 12 months. The primary efficacy outcome measured symptomatic recurrent VTE, comprising DVT and/or PE at 12 months.
The results showed a dramatic reduction in VTE recurrence. Symptomatic recurrent VTE occurred in only 1.3% of patients in the apixaban group compared with 10.0% in the placebo group, representing an 87% decrease in risk (hazard ratio 0.13; 95% confidence interval 0.04 to 0.36; p<0.001).
Safety Profile Remains Favorable
The safety analysis revealed reassuring bleeding rates. Major bleeding, defined according to the International Society on Thrombosis and Haemostasis criteria, occurred in just one patient (0.3%) who received apixaban and none who received placebo. Clinically relevant non-major bleeding was observed in 4.8% of patients in the apixaban group versus 1.7% in the placebo group, though this difference did not reach statistical significance (p=0.059).
Death occurred in one patient in the apixaban group and three in the placebo group, with no deaths attributed to cardiovascular or hemorrhagic causes. Adverse events other than bleeding or death occurred equally in both groups (2.0%).
Clinical Implications and Future Directions
Principal Investigator Dr. Gregory Piazza from Brigham and Women's Hospital explained the study's rationale: "Patients with acute VTE with transient provoking factors, such as surgery, trauma or immobility, typically receive short-term anticoagulation. However, the risk of VTE recurrence may remain high in certain patients with enduring risk factors, including those with obesity, chronic lung disease or autoimmune disorders."
The findings align with broader evidence supporting reduced-dose anticoagulation strategies. The RENOVE trial, published in The Lancet in March 2025, compared reduced-dose versus full-dose direct oral anticoagulants in 2,768 patients at high risk for VTE recurrence. While the reduced-dose strategy showed slightly higher recurrence rates (2.2% versus 1.8% over five years), it significantly reduced clinically relevant bleeding (9.9% versus 15.2%).
Dr. Piazza concluded that while low-intensity apixaban effectively reduced symptomatic VTE recurrence with low bleeding risk, "additional research is needed to identify which subgroups benefit most from extended anticoagulation." This personalized approach will be crucial for optimizing treatment duration and intensity in patients with provoked VTE and persistent risk factors.
