At one year, low-intensity apixaban therapy results in lower risk of symptomatic recurrent venous thromboembolism (VTE) compared to placebo in patients with provoked VTE and enduring risk factors. Furthermore, it carries a low risk of major bleeding, according to efficacy and safety results of the HI-PRO trial, presented during ESC Congress 2025 and simultaneously published Aug. 30 in NEJM.

In the single-center, double-blind trial, investigators Gregory Piazza, MD, FACC, et al., randomized 600 patients with VTE (mean age 60 years; 57% women; 19% non-White race) 1:1 to 12 months of twice-daily doses of 2.5 mg oral apixaban or placebo. Inclusion criteria included VTE after an occurrence of a transient provoking factor (most commonly surgery, immobility, trauma or acute medical illness); at least one enduring risk factor (most commonly inflammatory or autoimmune disorders, BMI ≥30, atherosclerotic cardiovascular disease or chronic lung disease); and at least three months of anticoagulation.

Results at one year showed that the primary efficacy outcome, first symptomatic recurrent VTE (a composite of deep-vein thrombosis, pulmonary embolism or both), occurred in four patients in the apixaban group and 30 patients in the placebo group (1.3% vs. 10%, hazard ratio [HR], 0.13; p<0.001).

The primary safety outcome, first episode of major bleeding, occurred in one patient in the apixaban group and none in the placebo group. Clinically relevant nonmajor bleeding occurred in 14 patients in the apixaban group and five patients in the placebo group (4.8% vs. 1.7%; HR, 2.68; p=0.06). No deaths attributed to cardiovascular or hemorrhagic causes occurred in either group. Nonhemorrhagic, nonfatal adverse events occurred in 2% of patients in each group.

While "current guidelines do not routinely recommend extended-duration anticoagulation for patients with provoked VTE," write Piazza, et al., "our results highlight a population with provoked VTE and enduring risk factors in which the risk of recurrence after the discontinuation of anticoagulation is high enough to warrant consideration of continued anticoagulation."

In an accompanying editorial comment, Neil A. Zakai, MD, writes that the trial "exposes the limits of our current VTE categories."

"We need to develop and validate models that integrate baseline risk factors, features of the acute event, bleeding risk, patient values, and clinician experience to determine who may benefit from extended VTE prevention," he adds. "The ‘provoked’ label should not end the conversation regarding the duration of anticoagulation; it should be the opening to an individualized patient-centered conversation."