Catheter-directed Thrombolysis for Iliofemoral DVT: Still No Magic Bullet

Post-thrombotic syndrome (PTS) occurs in 20 to 50 percent of patients after deep vein thrombosis (DVT) and may have a significant effect on quality of life. Independent predictors of PTS include recurrent ipsilateral DVT and extensive (iliac or common femoral) vein involvement.¹  Owing to the lack of effective therapies for PTS, there has been interest in catheter-directed thrombolysis (CDT) as a method of actively removing acute thrombus to quickly restore venous function and possibly prevent PTS (the “open-vein hypothesis”).² 

Prior randomized trials of CDT for acute proximal DVT have yielded conflicting results. In the CaVent study, patients undergoing CDT had lower rates of PTS at 24 months and five years compared with conventional anticoagulation therapy.^3,4  The more recent ATTRACT study, which used pharmacomechanical CDT, did not show a significant difference in PTS at 24 months but demonstrated significantly more major bleeding events in the CDT arm.⁵  However, a subsequent analysis of ATTRACT examining only those with more proximal (iliac or common femoral vein) involvement suggested that these patients had less moderate-to-severe PTS after receiving CDT.⁶ 

The CAVA study builds on these data by examining the use of ultrasound (US) -accelerated CDT as a means of facilitating clot dissolution. In this multicenter randomized trial, patients with an acute iliofemoral DVT (common femoral vein or more proximal) with symptom onset less than 14 days were randomized to standard anticoagulation therapy versus US-accelerated CDT. In the CDT arm, patients received a urokinase bolus plus infusion, given through a catheter that contained high-frequency US transducers for clot dissolution. Patients in the interventional arm were permitted to undergo other procedures per physician discretion including venous stenting and angioplasty. All patients received graduated compression stockings (30-40 mm Hg) within 24 hours. The primary outcome was the proportion of patients with PTS at 12 months (Villalta score ≥ 5 [5-9, mild; 10-14, moderate; 15+, severe or venous ulceration]).

Among 152 randomized patients who received the assigned therapy, there was no difference in PTS at 12 months (29% in CDT group vs. 35% in standard therapy group; overall response [OR], 0.75; 95% CI, 0.38-1.50; p=0.42). Major bleeding occurred in four patients (5%) receiving CDT compared with none in the standard group, with one such patient developing neuropraxia of the peroneal nerve. There was no significant difference in moderate to severe PTS between the two groups at 12 months. Recurrent DVT was similar between the two groups (6% CDT vs. 5% standard; OR, 1.23; 95% CI, 0.32-4.78). However, in-stent thrombosis occurred in 10 patients (13%) in the CDT arm. Patients mostly received either vitamin K antagonists (81-84%) or direct oral anticoagulants (DOACs; 8-16%).

This study did not show a reduction in PTS after providing additional US-accelerated CDT to standard anticoagulation therapy. These results align with those of the ATTRACT study, despite CAVA’s enrolment of patients who only had more proximal iliofemoral DVT. Several patients randomized to CDT underwent venous stenting, with a high rate of in-stent thrombosis despite therapeutic anticoagulation.

Limitations of this study included its long recruitment period (during which DOACs were introduced), short duration of follow-up, and high proportion of withdrawals or screening failures (about 15 patients per study arm). Moreover, the use of adjunctive techniques in the CDT arm, such as venous stenting and angioplasty, was not standardized and in some cases led to harm. Finally, this study only had 12 months of follow-up, and it is possible that PTS could develop over a longer period from the index event.