Catheter-Directed Venous Thrombolysis - CaVenT

Dec 19, 2011
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
South-Eastern Norway Regional Health Authority; Research Council of Norway; University of Oslo; Oslo University Hospital
Date Published:
01/01/2011
Date Updated:
12/19/2011
Original Posted Date:
12/19/2011
References

Description:

Acute iliofemoral deep vein thrombosis (DVT) is a fairly prevalent problem, which can be associated with significant morbidity, especially venous dysfunction resulting in post-thrombotic syndrome (PTS) (pain, swelling, a sensation of heaviness, edema, pigmentation, and deterioration of the skin, including venous ulcers in severe cases). The current trial sought to determine if catheter-directed thrombolysis would be of incremental benefit over routine management in reducing the incidence of PTS in patients with acute iliofemoral DVT.

Hypothesis:

Catheter-directed thrombolysis in addition to conventional treatment (anticoagulation, compression stockings) would be superior to conventional treatment alone in reducing the incidence of PTS in patients with acute iliofemoral DVT.

Study Design

  • Randomized
  • Parallel
  • Stratified

Patient Populations:

  • Age 18-75 years
  • Onset of symptoms within the past 21 days
  • Objectively verified (by diagnostic imaging) DVT localized in the upper half of the thigh, the common iliac vein, or the combined iliofemoral segment

    Number of enrollees: 189 (209 initially included)
    Duration of follow-up: 24 months
    Mean patient age: 52 years
    Percentage female: 37%

Exclusions:

  • Anticoagulant treatment before trial entry for more than the past 7 days
  • Contraindications to thrombolytic treatment, including bleeding diathesis
  • Indications for thrombolytic treatment—e.g., phlegmasia caerulea dolens or isolated vena cava thrombosis
  • Severe anemia (hemoglobin <80 g/L)
  • Thrombocytopenia (platelets <80 • 109/L)
  • Severe renal failure (estimated creatinine clearance <30 ml/min)
  • Severe hypertension—i.e., persistent systolic blood pressure higher than 160 mm Hg or
    diastolic blood pressure higher than 100 mm Hg
  • Pregnancy or thrombosis within 7 days postpartum
  • Less than 14 days post-surgery or post-trauma
  • History of subarachnoid or intracerebral bleeding
  • Disease with life expectancy <24 months
  • Drug misuse or mental disease that could interfere with treatment and follow-up
  • Former ipsilateral proximal DVT
  • Malignant disease needing chemotherapy
  • Any thrombolytic treatment within 7 days before trial inclusion

Primary Endpoints:

  • PTS at 24 months (assessed by the 33-point Villalta scale)
  • Iliofemoral patency at 6 months

Secondary Endpoints:

  • Frequency of clinically relevant bleeding related to catheter-directed thrombolysis
  • Recurrent venous thromboembolism (VTE) during follow-up
  • PTS at 6 months

Drug/Procedures Used:

Patients were randomized to initial low molecular weight heparin and warfarin followed by warfarin alone, with target international normalized ratio of 2.0-3.0, or to catheter-directed thrombolysis in addition to conventional treatment.

Concomitant Medications:

Daily elastic compression stockings at 24 months (56%)

Principal Findings:

A total of 189 patients were randomized, 99 to conventional treatment alone, and 90 to additional catheter-directed thrombolysis. Baseline characteristics were fairly similar between the two arms. The median duration of symptoms was 6.6 days. The majority of patients had femoral DVT (55%), and 61% had left-sided DVT. About a third of the patients had permanent risk factors for DVT, such as prior DVT (10%) and obesity (10%). About 24% of patients were heterozygous for factor V Leiden. Mean duration of catheter-directed thrombolysis was 2.4 days. Forty-three patients had complete thrombolysis with catheter-directed thrombolysis, and 37 had successful partial (50-99%) lysis. Adjunctive endovascular treatment was required in 39 patients, mostly balloon angioplasty.

While there was no difference in PTS at 6 months between the catheter-directed thrombolysis arm and conventional treatment arms (30.3% vs. 32.2%, p = 0.77), the primary outcome of PTS at 24 months was significantly lower in the catheter-directed thrombolysis arm (41.1% vs. 55.6%, p = 0.047). This corresponded to an absolute risk reduction of 14.4%, with a number needed to treat of seven patients. The other coprimary endpoint of iliofemoral patency at 6 months was also higher in the catheter-directed thrombolysis arm (65.9% vs. 47.4%, p = 0.012).

Bleeding complications were higher in the catheter-directed thrombolysis arm (20 events [3 major, 5 clinically relevant] vs. none). There were no deaths, pulmonary embolisms, or cerebral hemorrhages. Recurrent VTE events were lower in the catheter-directed thrombolysis arm (11% vs. 18%).

Interpretation:

The results of the CaVenT trial indicate that catheter-directed thrombolysis in addition to conventional treatment with anticoagulation and compression stockings was superior to conventional treatment alone in patients with acute iliofemoral DVT in reducing the incidence of PTS at 2 years, a condition associated with high morbidity.

This is an important trial, since most of the studies to date have compared systemic thrombolysis to conventional treatment, not focal catheter-directed thrombolysis. Those studies noted higher rates of bleeding than currently noted with catheter-directed thrombolysis. Thus, although the bleeding risk is still elevated, the results of this trial indicate that there should be an early consideration for catheter-directed thrombolysis in patients with acute iliofemoral DVT, especially if the clot burden is large.

Similar results had been noted in the recent TORPEDO trial. A larger trial (Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis [ATTRACT]) is ongoing.

References:

Enden T, Haig Y, Klow NE, et al. Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. Lancet 2011;Dec 13:[Epub ahead of print].

Keywords: Factor V, Stockings, Compression, Pulmonary Embolism, Heparin, Low-Molecular-Weight, Varicose Ulcer, Warfarin, Diagnostic Imaging, Postthrombotic Syndrome, Risk Factors, Edema, Pain, Pigmentation, Iliac Vein, Thrombosis, Venous Thrombosis, Obesity, Cerebral Hemorrhage


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