ATTRACT Journal Primer

WCVIS Authors: Tiffany Nakla, Roger Woolley, Kevin Zhou

Resident Editor: Isaac Levine, MD

Attending Editor: Suresh Vedantham, MD

Published 6/11/2025

ATTRACT

Pharmacomechanical Catheter-Directed Thrombolysis of Deep-Vein Thrombosis

Citation

Vedantham S, Goldhaber SZ, Julian JA, et al. Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis. N Engl J Med. 2017;377(23):2240-2252. doi:10.1056/NEJMoa1615066

Clinical Question

Does the addition of pharmacomechanical catheter-directed thrombolysis (PCDT) to anticoagulation reduce post-thrombotic syndrome (PTS) in patients with acute proximal deep vein thrombosis when compared with anticoagulation alone?

Main Clinical Finding

In this patient population, adding PCDT to anticoagulation does not significantly reduce the risk of post-thrombotic syndrome, but does increase the risk of major bleeding.

Major Takeaways

The addition of PCDT to anticoagulation does not significantly reduce the incidence of PTS compared to anticoagulation alone (47% of patients vs. 48%, p = 0.56) over 2 years. Furthermore, PCDT was associated with a higher risk of major bleeding (1.7% vs. 0.3%, p = 0.049) at 10 days.

PCDT did not significantly lower the rate of moderate-to-severe PTS (Villalta score ≥ 10) compared to the control group (18% of patients vs. 24%; p = 0.04) under the predefined significance threshold of p < 0.01 for secondary efficacy outcomes (more conservative to account for multiple testing). The severity of PTS, as measured by the Villalta score and Venous Clinical Severity Score (VCSS), was consistently lower in the PCDT group at all follow-up visits between 6 and 24 months, and these differences met the threshold for statistical significance (p ≤ 0.01) at most time points.

PCDT appeared to provide early symptom relief, with greater reductions in leg pain at 10 days (1.62 vs. 1.29 Likert points) and 30 days (2.17 vs. 1.83) compared to anticoagulation alone, but these improvements did not reach statistical significance (p = 0.02 and p = 0.03, respectively). Similarly, leg circumference showed greater reductions in the PCDT group at 10 days (0.26 cm decrease vs. 0.27 cm increase) and 30 days (0.74 cm vs. 0.28 cm), but these changes were not statistically significant (p = 0.02 and p = 0.05, respectively). There were no significant differences between groups in overall quality of life (SF-36, VEINES-QOL) or the rate of major non-PTS treatment failure.

These findings highlight that while PCDT may offer symptom relief, it does not significantly reduce PTS incidence and increases the short-term risk of major bleeding.

Study Type

Phase 3, multicenter, randomized, open-label, assessor-blinded controlled clinical trial.

Funding

National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH)

Boston Scientific

Covidien (now Medtronic)

Genentech

Arms

Control: Anticoagulation alone

Intervention: Anticoagulation and pharmacomechanical catheter-directed thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of tPA and thrombus aspiration or maceration, with or without stenting)

Primary Outcome

Development of post-thrombotic syndrome between 6 and 24 months of follow-up.

Post-thrombotic syndrome defined as:
- Villalta score of 5 or higher, OR
- New ulceration of the index leg between 6-24 months follow-up, OR
- Undergoing unplanned endovascular intervention due to severe venous symptoms within 6 months of treatment

Secondary Outcomes

Post-thrombotic syndrome (PTS) Severity (Villalta)
Treatment failure defined as any of the following:
- Unplanned endovascular procedure within 6 months
- Venous gangrene within 6 months
- Amputation within 24 months
Quality of life using SF-36, VEINES-QOL, Likert pain scale, and calf circumference
Thrombus removal quantified using a modified Marder score
Safety profile based on the incidence of bleeding, recurrent thromboembolism, and mortality

Inclusion Criteria

Symptomatic proximal DVT involving the iliac, common femoral, and/or femoral vein

Exclusion Criteria

Age < 16 years or > 75 years
Symptom duration of > 14 days of the DVT episode in the index leg (i.e. non-acute DVT)
In the index leg: established PTS, or previous symptomatic DVT within the last 2 years
In the contralateral (non-index) leg: symptomatic acute DVT involving the iliac and/or common femoral vein or for which thrombolysis is planned as part of initial therapy
Limb-threatening circulatory compromise
Pulmonary embolus with hemodynamic compromise (i.e. hypotension)
Inability to tolerate PCDT due to severe dyspnea or acute systemic illness
Allergy, hypersensitivity, or thrombocytopenia from heparin, tPA, or iodinated contrast, except for mild-moderate contrast allergies for which steroid premedication can be used
Hemoglobin < 9.0 mg/dl, INR > 1.6 before warfarin started, or platelets < 100,000 /ml
Moderate renal impairment in diabetic patients (estimated GFR < 60 ml/min) or severe renal impairment in non-diabetic patients (estimated GFR < 30 ml/min)
Active bleeding, recent (< 3 months) GI bleeding, severe liver dysfunction, bleeding diathesis
Recent (< 3 months) internal eye surgery or hemorrhagic retinopathy; recent (< 10 days) major surgery, cataract surgery, trauma, CPR, obstetrical delivery, or other invasive procedure
History of stroke or intracranial/intraspinal bleed, tumor, vascular malformation, aneurysm
Active cancer (metastatic, progressive, or treated within the last 6 months)
- Exception: Patients with non-melanoma primary skin cancers.
Severe hypertension on repeated readings (systolic > 180mmHg or diastolic > 105 mmHg)
Pregnancy (positive pregnancy test, women of childbearing potential must be tested)
Recent (within the past month) thrombolysis or participation in another investigational drug study
Use of a thienopryridine antiplatelet drug (except clopidogrel) within the last 5 days
Life expectancy of < 2 years or chronic non-ambulatory status
Inability to provide informed consent or to comply with study assessments (e.g. due to cognitive impairment or geographic distance)

Criticism

Large number of patients initially excluded, potentially affecting real-world validity

Relevance to VIR Field

ATTRACT demonstrated that PCDT, when compared to the standard of care in the treatment of venous thromboembolism of anticoagulation alone, did not reduce incidence of PTS. However, PCDT did appear to reduce PTS severity. Hence, further study into the effectiveness of PCDT and related therapies may be worthwhile.

Updates

Over a dozen additional studies have been published using data from the ATTRACT study. Subgroup analysis of iliofemoral deep vein thrombosis by Comerota et al. demonstrated that while PCDT did not reduce the incidence of PTS or recurrent venous thromboembolism, it did result in reduced PTS severity and improved venous disease-specific quality of life, with fewer patients experiencing moderate-to-severe PTS. Further analysis by Thukral et al. showed that patients with greater baseline symptoms derived the most significant benefits from PCDT.