Clinical and radiological outcomes of adjuvant catheter-directed thrombolysis of acute iliofemoral venous thrombosis compared to standard anticoagulant therapy: a randomized controlled study

Background
For many years, in the open vein hypothesis, it has been assumed that rapid thrombus elimination and restoration of unobstructed deep venous flow may prevent valvular reflux, venous obstruction, and postthrombotic syndrome (PTS); however, there is a controversy between trials about the validity of this hypothesis.
Objectives
To assess the benefit of adjuvant catheter-directed thrombolysis (CDT) in the prevention of PTS compared with standard therapy in patients with first-time iliofemoral deep-vein thrombosis.
Patients and methods
From January 2018 to October 2021, patients aged 18–70 years with a first-time iliofemoral deep venous thrombosis were recruited for this randomized controlled trial. Eligible patients with symptoms for no more than 21 days were randomly assigned to either adjuvant CDT with standard anticoagulation or standard anticoagulant treatment alone. PTS incidence as assessed by Villalta score at 12 months was the primary outcome of this study. Our secondary objectives were to describe the frequency of chronic postthrombotic changes, residual vein thrombosis, deep venous reflux, and deep venous thrombosis recurrence rates within 12 months of follow-up.
Results
At the completion of 12 months of follow-up, data were available for 92 patients (47 in the CDT group, 45 in the control group). Baseline characteristics and risk factors were comparable between the two groups. CDT was associated with a significant reduction of PTS incidence [10.6% in the CDT group and 31.1% in the control group; risk ratio (RR), 0.34; 95% confidence interval (CI), 0.13–0.87; =0.024]. Duplex ultrasound findings revealed statistically significant lower residual vein thrombosis in the CDT group [12.7% compared with 37.8% in the control group (RR 0.42; 95% CI, 0.22–0.77; =0.005); chronic postthrombotic vein changes were detected in 12.76% in CDT group versus 37.8% control group (RR 0.34; 95% CI, 0.14–0.78; =0.01]; deep venous reflux was significantly lower in CDT compared with standard treatment patients (8.5 vs. 24.4%; RR 0.31; 95% CI, 0.12–0.89; =0.03); thrombosis recurrence was comparable in the two treatment groups (4.25 vs. 11.1%) with no significant statistical difference (=0.023). Subgroups analysis revealed significantly increased risk of PTS among patients of residual vein thrombosis (RR 0.31; 95% CI, 0.11–0.89; =0.028), patients with chronic postthrombotic vein changes (RR 2.7; 95% CI, 1.25–5.8; =0.01), and deep venous reflux (RR 2.37; 95% CI, 1.07–5.24; =0.03). On the other hand, no significant correlation was detected between thrombosis recurrence and PTS (RR 1.42; 95% CI, 0.41–4.96; =0.57). Subgroups analysis also revealed increased risk of thrombosis recurrence among patients with residual vein thrombosis (RR 10.72; 95% CI, 1.35–85.33; =0.02).
Conclusion
The addition of CDT to anticoagulation resulted in a lower risk of PTS. CDT led to reduced late residual thrombus burden, chronic postthrombotic vein changes, and deep venous reflux. Duplex ultrasound changes including deep venous reflux, residual vein thrombosis, and chronic postthrombotic vein changes can be considered predictors for PTS.