Madrid, Spain – 30 August 2025: Apixaban 2.5 mg twice daily significantly reduced symptomatic venous thromboembolism (VTE) recurrence, with a low risk of major bleeding, in patients with provoked VTE and enduring risk factors, according to late-breaking research presented in a Hot Line session today at ESC Congress 2025 and simultaneously published in New England Journal of Medicine.1
People can develop a blood clot that blocks a vein (VTE) because of short-term factors, such as surgery or injury, or as a result of a chronic medical condition, such as cancer.
Explaining the rationale of the HI-PRO trial, Principal Investigator, Doctor Gregory Piazza from Brigham and Women's Hospital, Boston, USA, said: “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. In such patients, the optimal duration of anticoagulation is uncertain. We designed the HI-PRO trial to assess the efficacy and safety of extended-duration apixaban 2.5 mg twice daily, compared with placebo, for the prevention of recurrence in patients with provoked VTE and at least one enduring risk factor.”
The double-blind, randomised controlled HI-PRO trial was conducted at Brigham and Women’s Hospital. Eligible patients had deep vein thrombosis (DVT) or pulmonary embolism (PE) following a major provoking factor (e.g. major surgery or major trauma), had completed at least 3 months of standard-dose anticoagulation and had at least one enduring risk factor (e.g. body mass index [BMI] ≥30 kg/m2, chronic lung disease or chronic inflammatory disease). Patients were randomised 1:1 to apixaban 2.5 mg twice daily or placebo for 12 months. The primary efficacy outcome was symptomatic recurrent VTE, a composite of DVT and/or PE at 12 months. The principal safety outcome was major bleeding according to the International Society on Thrombosis and Haemostasis definition.
In total, 600 patients underwent randomisation. The mean age was 59.5 years and 57% were female. The most common provoking factors were surgery (33.5%), immobility (31.3%), trauma (19.2%) and acute medical illness (18.3%). The most common enduring risk factors were chronic inflammatory disorder (52.2%), BMI ≥30 kg/m2 (48.2%), atherosclerotic cardiovascular disease (29.3%) and chronic lung disease (22.3%).
Symptomatic recurrent VTE occurred in 1.3% of patients in the apixaban group compared with 10.0% in the placebo group, representing a significant 87% decrease (hazard ratio [HR] 0.13; 95% confidence interval [CI] 0.04 to 0.36; p<0.001). A secondary composite outcome of cardiovascular death, non-fatal myocardial infarction, stroke/transient ischaemic attack or systemic embolism, major adverse limb event, and coronary or peripheral ischaemia requiring revascularisation occurred with a similarly low frequency with apixaban and placebo (0.7% vs. 1.0%, respectively; HR 0.67; 95% CI 0.11 to 3.98).
Major bleeding occurred in 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 and 1.7% in the placebo group (HR 2.68; 95% CI 0.96 to 7.43; p=0.059). Death occurred in one patient in the apixaban group and three in the placebo group, with no deaths due to cardiovascular or haemorrhagic causes. Adverse events other than bleeding or death occurred in 2.0% of patients in both groups.
Doctor Piazza 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.”
ENDS