Key Points:
- Standard anticoagulation for provoked venous thromboembolism (VTE) is often discontinued after 3–6 months, but patients with enduring risk factors may remain at elevated risk for recurrence.
- The HI-PRO trial showed that extended use of low-intensity apixaban (2.5 mg twice daily) significantly reduced symptomatic VTE recurrence over 12 months compared to placebo.
- The intervention was well tolerated, with a low incidence of major bleeding.
Patients with provoked VTE (e.g. after surgery, trauma, or acute illness) typically receive short-term anticoagulation. However, many of these patients have persistent risk factors, such as obesity, chronic inflammatory conditions, or lung disease, and their long-term risk of recurrence remains unclear. The optimal strategy for extended anticoagulation in such individuals has not been firmly established.
Presented during a Hot Line session at ESC Congress 2025 and simultaneously published in the New England Journal of Medicine, the HI-PRO trial evaluated the safety and efficacy of extended low-dose apixaban in patients with provoked VTE and at least one enduring risk factor.
This double-blind, randomized trial enrolled 600 patients at Brigham and Women’s Hospital in Boston, USA. All participants had experienced a provoked deep vein thrombosis (DVT) or pulmonary embolism (PE), completed at least 3 months of standard-dose anticoagulation, and had at least one enduring risk factor (e.g., BMI ≥30 kg/m², chronic lung disease, chronic inflammatory disease). Patients were randomized 1:1 to receive apixaban 2.5 mg twice daily or placebo for 12 months.
The mean age was 59.5 years, and 57% of participants were women. The most common provoking factors included surgery (33.5%), immobility (31.3%), and trauma (19.2%). Enduring risk factors included chronic inflammatory conditions (52.2%) and obesity (48.2%).
Symptomatic recurrent VTE occurred in just 1.3% of the apixaban group versus 10.0% in the placebo group, representing an 87% relative risk reduction (HR 0.13; 95% CI 0.04–0.36; p<0.001). Major bleeding was rare, occurring in 0.3% of apixaban-treated patients and 0% in the placebo group. Clinically relevant non-major bleeding occurred in 4.8% vs. 1.7% of patients (HR 2.68; p=0.059). Deaths were infrequent and balanced between groups.
Dr. Gregory Piazza, the study’s principal investigator, concluded: “Low-intensity apixaban for 12 months effectively reduced symptomatic VTE recurrence with a low risk of major bleeding in patients with provoked VTE and enduring risk factors. Additional research is needed to identify which subgroups benefit most from extended anticoagulation.”
Funded by the Bristol-Myers Squibb/Pfizer Alliance, the HI-PRO trial provides important evidence supporting extended, low-dose anticoagulation in patients traditionally considered low risk after a provoked VTE but who have persistent comorbidities that elevate recurrence risk.
