HI-PRO Trial: Extended Low-Dose Apixaban Prevents Recurrence in Provoked VTE with Enduring Risk Factors

Venous thromboembolism (VTE) remains a major contributor to morbidity and mortality worldwide. Traditionally, events are categorized as provoked (triggered by surgery, trauma, or immobility) or unprovoked, with current guidelines recommending limited anticoagulation for provoked VTE due to a perceived lower recurrence risk. However, the presence of enduring risk factors such as obesity, chronic lung disease, or autoimmune conditions may increase recurrence rates, raising uncertainty about the optimal treatment duration.

The HI-PRO trial, published in The New England Journal of Medicine in August 2025, addressed this gap. In this double-blind study, 600 patients with provoked VTE plus at least one enduring risk factor were randomized to receive apixaban 2.5 mg twice daily or placebo for 12 months after completing initial anticoagulation.

Results showed a marked reduction in recurrent VTE: only 1.3% of patients on apixaban experienced symptomatic recurrence versus 10.0% with placebo (HR 0.13; 95% CI 0.04–0.36; p<0.001). Major bleeding was rare (1 case in the apixaban arm, none in placebo), while clinically relevant nonmajor bleeding occurred in 4.8% versus 1.7% (HR 2.68; 95% CI 0.96–7.43; p=0.06). Mortality was low and balanced between groups, with no cardiovascular or hemorrhagic deaths.

These findings highlight that patients with provoked VTE but enduring risk factors face recurrence rates approaching those of unprovoked VTE, and that extended low-dose apixaban can provide substantial protection with an acceptable safety profile. The results challenge the traditional dichotomy of provoked versus unprovoked VTE and support reconsideration of long-term anticoagulation strategies in this underrepresented population.

#Hematology #Thrombosis #Apixaban #VTE #NEJM

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