CAVA (Ultrasound‐Accelerated Catheter‐Directed Thrombolysis on Preventing Post‐Thrombotic Syndrome) Trial: Long‐Term Follow‐Up Results

Abstract

Background The CAVA (Ultrasound‐Accelerated Catheter‐Directed Thrombolysis Versus Anticoagulation for the Prevention of Post‐Thrombotic Syndrome) trial did not show a reduction of post‐thrombotic syndrome (PTS) after additional ultrasound‐accelerated catheter‐directed thrombolysis in patients with acute iliofemoral deep vein thrombosis at 1‐year follow‐up. This prespecified analysis of the CAVA trial aimed to determine the impact of additional thrombolysis on outcomes of PTS at long‐term follow‐up. Methods and Results Patients aged 18 to 85 years with a first‐time acute iliofemoral deep vein thrombosis were included and randomly assigned (1:1) to either standard treatment plus ultrasound‐accelerated catheter‐directed thrombolysis or standard treatment alone. The primary outcome was the proportion of PTS (Villalta score ≥5 on 2 occasions ≥3 months apart or venous ulceration) at the final follow‐up visit. Additionally, PTS according to the International Society on Thrombosis and Haemostasis (ISTH) consensus definition was assessed to allow external comparability. Major bleedings were the main safety outcome. At a median follow‐up of 39.0 months (interquartile range, 23.3–63.8), 120 patients (79.8%) participated in the final follow‐up visit: 62 from the intervention group and 58 from the standard treatment group. PTS developed in 19 (30.6%) versus 26 (44.8%) patients, respectively (odds ratio [OR], 0.54; 95% CI, 0.26 to 1.15 [ P =0.11]), with an absolute difference between groups of −14.2% (95% CI, −32.0% to 4.8%). Using the ISTH consensus definition, a significant reduction in PTS was observed (29 [46.8%] versus 40 [69.0%]) (OR, 0.40; 95% CI, 0.19–0.84 [ P =0.01]) with an absolute difference between groups of −22.2% (95% CI, −39.8% to −2.8%). No new major bleedings occurred following the 12‐month follow‐up. Conclusions The impact of additional ultrasound‐accelerated catheter‐directed thrombolysis on the prevention of PTS was found to increase with time. Although this study was limited by its sample size, the overall findings indicate a reduction of mild PTS without impact on quality of life. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00970619.

Efficacy of ultrasound assisted catheter-directed thrombolysis compared to catheter-directed thrombolysis in vitro

“…The age of in vivo thrombus is highly variable; therefore, the effect of US-CDT can be masked as a result of small sample sizes with older thrombi in general and/or uneven distribution of thrombus age in the different cohorts. Although pulmonary embolism is an acute event and, in many cases, clinically immediately apparent, formation of the thrombus has begun earlier, suggesting a higher thrombus age in clinical trials such as the CAVA trail in comparison to our present in vitro study (20).…”

“…The findings did not necessary translate into clinical studies and medium-term outcome studies for ilio-femoral deep venous thrombosis as described by Engelberger et al (16,17). Recent results from the CAVA trial suggest a potential benefit regarding long-term effects but the relevance of US-CDT remains controversial (18)(19)(20). Similarly, in pulmonary embolism, the improved efficacy of US-CDT published in in vitro studies did not translate into clinical trials (21).…”

New perspectives for prevention of the post-thrombotic syndrome

“…However, in a prespecified subgroup analysis the incidence of moderate/severe PTS was found to be lower in the subgroup of patients with ilio-femoral thrombosis. 13 The results of the ATTRACT study are consistent with those of two additional smaller clinical trials, the CAVENT 14,15 and the DUTCH CAVA, 16,17 and suggest that CDT cannot be recommended on a routine basis because of its invasiveness, the associated risk of major bleedings and the uncertainty about its efficacy. At present, it can be considered only in patients with threatening clinical presentation provided the ilio-femoral tract is involved and the bleeding risk is low, in centers where adequate expertise and resources are available.…”

How to optimize the prevention of post-thrombotic syndrome: recent advances

“…after five years [29,30]. The CAVA [31] trial in patients with iliofemoral DVT did not find significantly less PTS after one year, although using the ISTH consensus definition a significant 22% absolute reduction in PTS was observed after a median follow-up of 39 months [32]. Finally, the ATTRACT trial in patients with proximal DVT did not find any difference in PTS after two years [33], although CDT did lower PTS severity in patients with iliofemoral DVT [34].…”