Elsevier

The Lancet

Volume 379, Issue 9810, 7–13 January 2012, Pages 31-38
The Lancet

Articles
Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial

https://doi.org/10.1016/S0140-6736(11)61753-4Get rights and content

Summary

Background

Conventional anticoagulant treatment for acute deep vein thrombosis (DVT) effectively prevents thrombus extension and recurrence, but does not dissolve the clot, and many patients develop post-thrombotic syndrome (PTS). We aimed to examine whether additional treatment with catheter-directed thrombolysis (CDT) using alteplase reduced development of PTS.

Methods

Participants in this open-label, randomised controlled trial were recruited from 20 hospitals in the Norwegian southeastern health region. Patients aged 18–75 years with a first-time iliofemoral DVT were included within 21 days from symptom onset. Patients were randomly assigned (1:1) by picking lowest number of sealed envelopes to conventional treatment alone or additional CDT. Randomisation was stratified for involvement of the pelvic veins with blocks of six. We assessed two co-primary outcomes: frequency of PTS as assessed by Villalta score at 24 months, and iliofemoral patency after 6 months. Analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00251771.

Findings

209 patients were randomly assigned to treatment groups (108 control, 101 CDT). At completion of 24 months' follow-up, data for clinical status were available for 189 patients (90%; 99 control, 90 CDT). At 24 months, 37 (41·1%, 95% CI 31·5–51·4) patients allocated additional CDT presented with PTS compared with 55 (55·6%, 95% CI 45·7–65·0) in the control group (p=0·047). The difference in PTS corresponds to an absolute risk reduction of 14·4% (95% CI 0·2–27·9), and the number needed to treat was 7 (95% CI 4–502). Iliofemoral patency after 6 months was reported in 58 patients (65·9%, 95% CI 55·5–75·0) on CDT versus 45 (47·4%, 37·6–57·3) on control (p=0·012). 20 bleeding complications related to CDT included three major and five clinically relevant bleeds.

Interpretation

Additional CDT should be considered in patients with a high proximal DVT and low risk of bleeding.

Funding

South-Eastern Norway Regional Health Authority; Research Council of Norway; University of Oslo; Oslo University Hospital.

Introduction

Acute deep vein thrombosis (DVT) of the lower limbs occurs in about 1·0 person per 1000 population per year and is associated with substantial morbidity.1 International guidelines for antithrombotic therapy form the basis of adequate treatment.2 Although anticoagulation effectively prevents thrombus extension, pulmonary embolism, death, and recurrence, many patients develop venous dysfunction resulting in post-thrombotic syndrome (PTS). This syndrome is characterised by pain, swelling, a sensation of heaviness, oedema, pigmentation, and deterioration of the skin, including venous ulcers in severe cases.3 PTS is associated with reduced individual health-related quality of life and a substantially increased economic burden.4, 5, 6

About 80% of symptomatic DVT of the lower limbs affects the popliteal and more proximal veins.7 After adequate anticoagulation, nearly half of these patients develop some degree of PTS.8 Daily use of elastic compression stockings (class II, 30 mm Hg) reduces the risk of PTS by about 50%.8, 9 However, even with recommended treatment, around one in four patients is at risk of a chronically impaired long-term outcome, and improved treatment to reduce PTS development is greatly needed.

PTS probably evolves from venous obstruction, venous incompetence caused by inflammatory destruction of the venous valves in response to the acute thrombotic occlusion, or both.3 A recent systematic review10 suggested that accelerated removal of thrombus material by systemic thrombolysis can prevent vein dysfunction and PTS, but such treatment was associated with an unacceptable risk of bleeding. Catheter-directed thrombolysis (CDT) is a novel modality in which a catheter is introduced into the affected vein and advanced through the thrombotic segment. Multiple side-holes enable delivery of a thrombolytic agent directly into the clots, and reduced doses of thrombolytic agents are used. Several case series have shown effective lysis and promising results; however, the net clinical effect and safety have not been documented in clinical trials. The Catheter-directed Venous Thrombolysis (CaVenT) study aimed to evaluate whether additional CDT for acute iliofemoral vein thrombosis improved long-term outcomes by reducing the risk of PTS.

Section snippets

Study design and participants

The CaVenT Study was a Norwegian, multicentre, open-label, randomised controlled trial of the efficacy and safety of additional CDT with alteplase in patients with a first-time acute iliofemoral DVT. Patients aged 18–75 years with an objectively verified DVT above mid-thigh level and symptom duration up to 21 days were eligible for inclusion. Patients were ineligible if an increased risk of bleeding or other exclusion criteria were present (panel 1). The study was approved by the Regional

Results

During January, 2006, to December, 2009, 209 patients were recruited from 20 centres within eight hospital trusts of the South-Eastern Norway Regional Health Authority (figure). During the trial, screening logs were recorded for 613 patients admitted with VTE at two of the main study sites, which contributed 61 (29%) of all 209 trial patients (Fredrikstad and Ullevål). The main reasons for exclusion were DVT below mid-thigh (n=209) or in other locations (n=77), age older than 75 years (n=78) or

Discussion

This randomised trial was the first to show a clinically significant reduction in PTS after additional CDT compared with conventional treatment alone. The absolute risk reduction was 14·4% and treatment of seven patients was needed to prevent one PTS, but CDT entailed a small additional risk of bleeding. We believe that this effect is clinically relevant and is a significant improvement in the prevention of PTS after severe DVT (panel 3).

The frequency of PTS in our study was slightly higher

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