article228

ATTRACT

"Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis".The New England Journal of Medicine. 2017. 377(23):2240-2252.PubMed•Full text•PDF

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcome
8.2 Secondary Outcomes
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

In patients with acute proximal deep-vein thrombosis, does the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation reduce the risk of the post-thrombotic syndrome?

Bottom Line

Among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not reduce the risk of the post-thrombotic syndrome but increased the risk of major bleeding.

Major Points

The post-thrombotic syndrome, a frequent complication of proximal deep-vein thrombosis, can cause long-term pain, swelling, and ulcers in the affected limb. Pharmacomechanical catheter-directed thrombolysis (CDT), involving the intrathrombus delivery of thrombolytic drugs and mechanical thrombus removal, was hypothesized to reduce the risk of post-thrombotic syndrome.

Guidelines

As of the current knowledge cutoff date, there are no updated guidelines reflecting the results of this trial.

Design

Multicenter, randomized, open-label, assessor-blinded, controlled clinical trial.
N=692 patients with acute proximal deep-vein thrombosis randomized into two groups:
- Pharmacomechanical CDT plus anticoagulation (n=337)
- Anticoagulation alone (control group) (n=355)
Setting: 56 clinical centers in the United States
Enrollment: 2009-2014
Mean follow-up: 24 months
Analysis: Modified intention-to-treat
Primary outcome: Development of the post-thrombotic syndrome between 6 and 24 months

Population

Inclusion Criteria

- Symptomatic proximal deep-vein thrombosis involving the femoral, common femoral, or iliac vein.
- Age 16 to 75 years not pregnant, within 14 days of symptom onset, and without high bleeding risk or established post-thrombotic syndrome.

Exclusion Criteria

- Patients younger than 16 or older than 75 years, pregnant individuals, high bleeding risk, active cancer, established post-thrombotic syndrome, or ipsilateral deep-vein thrombosis in the previous 2 years.

Baseline Characteristics

- Well-matched between treatment groups.

Interventions

- Anticoagulant therapy consistent with published guidelines.
- Pharmacomechanical CDT involved intrathrombus administration of recombinant tissue plasminogen activator (rt-PA), thrombus aspiration/maceration (with or without stenting).

Outcomes

Primary Outcome

- No significant difference in the post-thrombotic syndrome development between CDT (47%) and control (48%) groups (RR 0.96; 95% CI, 0.82 to 1.11; P=0.56).

Secondary Outcomes

- More early major bleeds within 10 days in CDT group (1.7% vs. 0.3%, P=0.049).
- No significant difference in recurrent venous thromboembolism over 24 months between groups (12% CDT vs. 8% control, P=0.09).
- Moderate-to-severe post-thrombotic syndrome less in CDT group (18% vs. 24%, RR 0.73; 95% CI, 0.54 to 0.98; P=0.04).
- Less severe post-thrombotic syndrome scores in CDT group across all follow-up points (P<0.01).
- No significant difference in quality of life improvement between groups from baseline to 24 months.

Criticisms

- Missing data may have led to an underestimate of treatment effects.
- Limited power for subgroup analysis.

Funding

National Heart, Lung, and Blood Institute, Boston Scientific, Covidien (now Medtronic), Genentech, Society of Interventional Radiology Foundation, and others. Compression stockings were donated by BSN Medical.