Association of Successful Ultrasound-Accelerated Catheter-Directed Thrombolysis with Postthrombotic Syndrome: A Post Hoc Analysis of the CAVA Trial

Abstract

Background The CAVA trial did not show the anticipated risk reduction for postthrombotic syndrome (PTS) after thrombus removal via additional ultrasound-accelerated catheter-directed thrombolysis (UACDT) in patients with acute iliofemoral deep vein thrombosis (IFDVT). Difficulties in achieving an effective degree of recanalization through thrombolysis may have influenced outcomes. We therefore assessed whether successful UACDT (restored patency ≥ 90%) did reduce the development of PTS. Methods This CAVA trial post hoc analysis compared the proportion of PTS at 1-year follow-up between patients with successful UACDT and patients that received standard treatment only. In addition, clinical impact as well as determinants of successful thrombolysis were explored. Results UACDT was initiated in 77 (50.7%) patients and considered successful in 41 (53.2%, interrater agreement κ = 0.7, 95% confidence interval 0.47–0.83). PTS developed in 15/41 (36.6%) patients in the successful UACDT group versus 33/75 (44.0%) controls (p = 0.44). In this comparison, successful UACDT was associated with lower Venous Clinical Severity Score (3.50 ± 2.57 vs. 4.82 ± 2.74, p = 0.02) and higher EuroQOL-5D (EQ-5D) scores (40.2 ± 36.4 vs. 23.4 ± 34.4, p = 0.01). Compared with unsuccessful UACDT, successful UACDT was associated with a shorter symptom duration at inclusion (p = 0.05), and higher rates of performed adjunctive procedures (p < 0.001) and stent placement (p < 0.001). Conclusion Successful UACDT was not associated with a reduced proportion of PTS 1 year after acute IFDVT compared with patients receiving standard treatment alone. There was, however, a significant reduction in symptom severity and improvement of generic quality of life according to the EQ-5D. Better patient selection and optimization of treatment protocols are needed to assess the full potential of UACDT for the prevention of PTS. Trial Registration Number ClinicalTrials.gov number, NCT00970619.

Visualizing thrombosis to improve thrombus resolution

“…It was shown that pulsed cavitational ultrasound therapy was able to recanalize noninvasively in an in vitro model of acute venous thrombosis 120 . A post hoc analysis of the CAVA (ultrasound‐accelerated catheter‐directed thrombolysis versus anticoagulation for the prevention of post‐thrombotic syndrome) trial of risk for postthrombotic syndrome after early thrombus removal via additional ultrasound‐accelerated, catheter‐directed thrombolysis in patients with acute iliofemoral DVT showed a significant reduction in symptom severity and improvement of generic quality of life 121 . One study of a PE response team investigated the use of catheter‐directed thrombolysis versus systemic intravenous thrombolysis or thrombectomy 122 .…”

“…120 A post hoc analysis of the CAVA (ultrasound-accelerated catheter-directed thrombolysis versus anticoagulation for the prevention of post-thrombotic syndrome) trial of risk for postthrombotic syndrome after early thrombus removal via additional ultrasound-accelerated, catheter-directed thrombolysis in patients with acute iliofemoral DVT showed a significant reduction in symptom severity and improvement of generic quality of life. 121 One study of a PE response team investigated the use of catheter-directed thrombolysis versus systemic intravenous thrombolysis or thrombectomy. 122 A study of patients with acute ischemic stroke undergoing thrombolysis showed that low α2-plasmin inhibitor antigen levels on admission is an independent predictor of unfavorable long-term outcomes.…”

The efficacy of rotational pharmaco-mechanical thrombectomy in patients with acute iliofemoral deep vein thrombosis: Is the standard treatment of deep vein thrombosis changing?

“…30 In contrary to these results, CAVA trial showed that there was no significant reduction of PTS following ultrasound-accelerated catheter-directed thrombolysis in patients with acute iliofemoral DVT. 31 The risk of PTS was not significantly different when compared with standard therapy after 1 year of acute iliofemoral DVT. 32 The ATTRACT trial, compared Pharmaco-mechanical thrombolysis plus standard therapy and standard anticoagulant therapy alone in patients with acute DVT at the femoropopliteal segments and proximal iliac segments.…”

Antithrombotics and new interventions for venous thromboembolism: Exploring possibilities beyond factor IIa and factor Xa inhibition

“…A post hoc analysis of the Catheter Versus Anticoagulation Alone for Acute Primary (Ilio)Femoral DVT (CAVA) trial focused on the effect of ultrasound-accelerated catheter-directed thrombolysis on the development of the postthrombotic syndrome after 1 year of follow-up; although the risk was not reduced after successful thrombolysis for acute iliofemoral DVT, these patients did report an improvement in the quality of life. 91 Finally, observational data suggest that endovascular treatment of postthrombotic syndrome with stent placement might improve mid-and long-term clinical (functional) scores. 92,93 The Aspirin Plus Rivaroxaban Versus Rivaroxaban…”