Additional ultrasound-accelerated catheter-directed thrombolysis (CDT) does not change the risk of post-thrombotic syndrome in patients with acute iliofemoral deep vein thrombosis (DVT) at one-year follow up, compared with standard therapy alone, according to findings of the CAVA trial published in November 2019 in The Lancet Haematology. However, 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 iliofemoral DVT.
Examined in presentations by both Pascale Notten and Cees Wittens (Maastricht, The Netherlands)—winners of the best abstract session at the International Union of Phlebology chapter meeting (UIP; 25–27 August, Krakow, Poland)—results of the CAVA trial also showed a high rate of thrombotic events, mostly due to in-stent thrombosis.
Notten et al write: “Between May 2010, and September 2017, 184 patients were randomly assigned to either additional ultrasound-accelerated CDT (n=91) or standard treatment alone (n=93). Exclusion because of screening failure or early withdrawal of informed consent resulted in 77 patients in the intervention group and 75 in the standard treatment group starting allocated treatment.
“Median follow-up was 12 months (IQR 6–12). Twelve-month post-thrombotic syndrome occurred in 22 (29%) patients allocated to additional treatment versus 26 (35%) patients receiving standard treatment alone (odds ratio 0.75 [95% CI 0.38–1.50]; p=0.42). Major bleeding occurred in four (5%) patients in the intervention group, with associated neuropraxia or the peroneal nerve in one patient, and no events in the standard treatment group. No serious adverse events occurred. None of the four deaths (one [1%] in the intervention group vs. three [4%] in the standard treatment group) were treatment related.”
Furthermore, as reported in The Lancet Haematology, a total of 24 thrombotic events occurred in 20 patients. Eighteen per cent (n=14) of patients from the intervention group developed 17 events versus seven events in 8% (n=6) of patients from the control group (p=0.06). Of the 17 thrombotic events which were seen in the intervention group, more than 70% (12 out of 17) were due to in-stent thrombosis.
Speaking to Venous News about the findings of the CAVA trial, Notten says: “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 the ATTRACT trial and show no statistically significant difference between treatment groups as opposed to the CaVenT trial.
“With the CAVA trial, 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?
A subgroup analysis of the results, presented by Wittens at UIP, aimed to assess the success rate of additional ultrasound-accelerated CDT in restoring patency (to 90% or more), and its relation to the development of post-thrombotic syndrome at one year. Wittens explained: “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 CDT might depend on its ability to achieve successful recanalisation.”
According to the preliminary analysis, recanalisation was considered successful in 53% of patients (41 out of 77) who received additional ultrasound-accelerated CDT, while a total of 75 patients in the CAVA trial received standard treatment only. Overall, post-thrombotic syndrome developed in 22% of patients (n=9) from the successful thrombolysis subgroup, and 35% (n=26) of the patients from the control group (p=0.15).
Comparing the successful thrombolysis subgroup 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, favouring those who were successfully treated.
Based on the findings of the subgroup analysis, said Wittens, successful thrombolysis does result in benefits such as a lower severity of symptoms and improved quality of life for patients when considering multiple aspects. Commenting on these results, Wittens added: “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 received a successful intervention.”
He concluded: “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.”