Extended low-dose apixaban could reduce symptomatic superficial vein thrombosis in patients with provoked venous thromboembolism and persistent risk factors, according to a post hoc analysis of the HI-PRO randomized clinical trial.
The HI-PRO trial was a double-blind, placebo-controlled study involving adult patients with provoked deep vein thrombosis or pulmonary embolism who had completed at least 3 months of prior anticoagulation therapy and had at least one ongoing risk factor for recurrence, including obesity, chronic inflammatory or autoimmune disease, atherosclerotic cardiovascular disease, or persistent immobility. The patients were randomly assigned to receive either apixaban, 2.5 mg twice daily, or placebo for the duration of the study period. The study population had a mean age of 60 years, and 57% were female.
In the analysis of 600 patients, researchers determined that primary outcome of first symptomatic superficial vein thrombosis occurred in 1.3% (n = 4) of the patients receiving apixaban compared with 4.3% (n = 13) of those receiving placebo over a period of 12 months, representing a 70% lower likelihood of experiencing the events with low-dose apixaban compared with placebo.
Concomitant deep vein thrombosis or pulmonary embolism occurred in 0.3% (n = 1) of the patients receiving apixaban and 2% (n = 5) of those receiving placebo. All such patients required therapeutic anticoagulation and unanticipated clinical evaluation.
The secondary outcome of first isolated symptomatic superficial vein thrombosis without concomitant venous thromboembolism occurred in 1% (n = 3) of the patients receiving low-dose apixaban and 2.7% (n = 8) of those receiving placebo, equivalent to a lower likelihood of events that didn't reach statistical significance.
All isolated superficial vein thrombosis events were symptomatic, required unanticipated clinical evaluation. Most cases were treated with anticoagulation, while the rest underwent conservative management.
Superficial vein thrombosis shares pathophysiologic features with deep vein thrombosis and pulmonary embolism and may precede or coexist with these conditions, the researchers noted.
The analysis was limited because the trial wasn't designed or powered to detect differences in superficial vein thrombosis outcomes, and the number of events was small. The insignificant secondary outcome and limited statistical power could constrain generalizability, and the findings should be considered hypothesis generating.
Despite these limitations, the randomized design and complete follow-up supported the internal validity of the findings.
“[E]xtended low-intensity anticoagulation with apixaban was associated with a reduction in symptomatic [superficial vein thrombosis],” wrote lead study author Sina Rashedi, MD, MPH, of the Thrombosis Research Group at Brigham and Women’s Hospital and Harvard Medical School, and colleagues, adding that further randomized clinical trials focused on this outcome are needed.
Source: JAMA Cardiology
