Additional ultrasound-accelerated catheter-directed thrombolysis does not lower the risk of post-thrombotic syndrome in patients with acute iliofemoral deep-vein thrombosis (DVT), according to findings of the CAVA trial presented at the International Union of Phlebology chapter meeting (UIP 2019; 25–27 August, Krakow, Poland). Preliminary results of a post-hoc subgroup analysis suggest that if recanalisation is successful, post-thrombotic syndrome is less severe and quality of life scores are higher one year after an acute DVT.
Examined in presentations by both Pascale Notten (Maastricht, the Netherlands) and Cees Wittens (Maastricht, the Netherlands)—winners of the best abstract session at UIP— and published in The Lancet Haematology, results of the CAVA trial also showed a high rate of thrombotic events, mostly due to in-stent thrombosis.
Post-thrombotic syndrome is a common long-term complication of deep-vein thrombosis , particularly in cases where the localisation of the thrombus is iliofemoral or more cranial. The ‘open vein hypothesis’ suggests early removal of the thrombus as a means of preserving venous function and restoring venous outflow, thereby preventing the development of post-thrombotic syndrome; ultrasound-accelerated catheter-directed thrombolysis was considered a promising option for this removal.
As part of the multicentre, randomised controlled CAVA trial, which aimed to determine whether additional ultrasound-accelerated catheter-directed thrombolysis can decrease the risk of post-thrombotic syndrome, 184 patients with a first-time acute iliofemoral deep-vein thrombosis were randomly assigned to one of two treatment groups; either standard post-thrombotic treatment with additional ultrasound-accelerated catheter-directed thrombolysis or standard treatment (including early anticoagulant therapy, compression therapy, and mobilisation) alone.
Results of the trial showed that post-thrombotic syndrome occurred in 22 of the 77 patients (29%) randomised to the additional thrombolysis group, compared to 26 out of 75 patients (35%) in the standard treatment cohort (odds ratio 0.75, 95%CI, 0.38-1.50, p=0.42). Major bleeding occurred in four patients (5%) from the intervention group, compared to none in the control group, (p=0.06). Furthermore, a total of 24 thrombotic events occurred in 20 patients: 14 patients (18%) from the intervention group developed 17 events versus seven events in six patients (8%) from the control group (P=0.06). Of the 17 thrombotic events in the intervention group, more than 70% (12 out of 17) were due to in-stent thrombosis.
Speaking to Venous News about the results, presenter Notten said: “When comparing our results to the two previous large trials (CaVenT and ATTRACT), our outcomes regarding the development of post-thrombotic syndrome are similar to those found in the ATTRACT trial and show no statistically significant difference between treatment groups as opposed to the CaVenT trial.
“With the CAVA trial being inconclusive, the discussion regarding the role of additional catheter-directed thrombolysis in the treatment of acute iliofemoral deep-vein thrombosis persists. Further research including optimising patient selection, interventional techniques, and peri-interventional treatment regimens is essential.”
Can successful thrombolysis prevent post-thrombotic syndrome?
Presented by Wittens at UIP, a sub-group analysis of the results aimed to assess the success rate of additional ultrasound-accelerated catheter-directed thrombolysis in restoring patency (to 90% or more) and its relation to development of post-thrombotic syndrome at one year. As the degree of residual vein occlusion correlates with the risk of post-thrombotic syndrome, it has been said that the preventative impact of ultrasound-accelerated catheter-directed thrombolysis might depend on its ability to achieve successful recanalisation.
According to the preliminary analysis, recanalisation was considered successful in 41 out of the 77 patients (53%) who received additional ultrasound-accelerated catheter-directed thrombolysis, while a total of 75 patients in the CAVA trial received standard treatment only. Overall, post-thrombotic syndrome developed in nine patients (22%) from the successful thrombolysis subgroup and 26 (35%) of the control patients (P=0.15).
Comparing the successful thrombolysis sub-group to those who underwent unsuccessful thrombolysis—post-thrombotic syndrome developed in 13 out of 36 patients (37%) —no significant difference in proportion of post-thrombotic syndrome was seen (p=0.17). However, the severity was significantly lower in those successfully treated. Generic and disease-specific quality of life questionnaires also differed significantly between groups, once again favouring those who had been successfully treated.
Based on the findings of the sub-group analysis, successful thrombolysis does result in benefits such as less severe symptoms and improved quality of life when considering multiple aspects. Commenting on these results, Cees Wittens said to Venous News: “The subgroup analysis shows that proper quality control of an intervention is essential to evaluate an intended treatment. Unfortunately, this trial shows that only 53% of the patients who received the intervention had a successful intervention.
“Since the preliminary subgroup analysis showed a significant improvement in clinical scores and quality of life in those successfully recanalised, the overall conclusion of the various trials should not be that early thrombus removal is not effective in achieving better clinical outcomes and that this treatment should be abandoned; it tells us that early thrombus removal actually has the capacity to limit long-term post-thrombotic morbidity, if only we are able to improve the process of patient selection and develop better interventional treatments.”