Two-Year Data From ATTRACT Trial of Catheter-Directed Thrombolysis for DVT Published in NEJM
December 6, 2017—The 2-year follow-up data from the Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis (ATTRACT) clinical trial have been published by Suresh Vedantham, MD, et al in The New England Journal of Medicine (NEJM; 2017;377:2240–2252).
The ATTRACT trial evaluated pharmacomechanical catheter-directed thrombolysis for deep vein thrombosis (DVT). In the trial, pharmacomechanical thrombolysis was hypothesized to reduce the risk of the postthrombotic syndrome that frequently develops in patients with proximal DVT despite treatment with anticoagulant therapy.
In comments to Endovascular Today upon the NEJM publication, Dr. Vedantham noted that the ATTRACT trial is the first large, United States–based multicenter randomized trial to evaluate modern endovascular therapy for acute DVT treatment and was conducted under National Institutes of Health and US Food and Drug Administration auspices with high methodological production values and unprecedented precautions against bias.
The 2-year ATTRACT data were first presented in March 2017 at the Society of Interventional Radiology annual scientific meeting. An expanded overview of the presentation with expert commentary was published in the April 2017 issue of Endovascular Today (2017:16:46–49).
As published in NEJM, 692 patients with acute proximal DVT were randomized to receive either anticoagulation alone (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting). The primary outcome was the development of the postthrombotic syndrome between 6 and 24 months of follow-up.
The investigators reported that between 6 and 24 months, there was no significant between-group difference in the percentage of patients with postthrombotic syndrome (47% in the pharmacomechanical thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval, 0.82–1.11; P = .56).
Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs 0.3% of patients; P = .049), but no significant difference in recurrent venous thromboembolism was seen over the 24-month follow-up period (12% in the pharmacomechanical thrombolysis group and 8% in the control group; P = .09).
Moderate-to-severe postthrombotic syndrome was observed in 18% of patients in the study group versus 24% of those in the control group (risk ratio, 0.73; 95% confidence interval, 0.54–0.98; P = .04). Severity scores for postthrombotic syndrome were lower in the study group at 6, 12, 18, and 24 months of follow-up (P < .01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life (QOL) was similar between the groups.
The investigators concluded that among patients with acute proximal DVT, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of postthrombotic syndrome but did result in a higher risk of major bleeding.
Contextualizing the significance of ATTRACT in comments to Endovascular Today, Dr. Vedantham stated, "The study was successful in being completed with enrollment of its full target population. The study was focused on determining, against the background of the known risks of thrombolytic therapy, if there is a compelling justification to extend this more aggressive treatment approach to routine first-line use in patients with above-popliteal DVT and low bleeding risk. The study successfully answered this question, clearly finding that this standard was not met."
Dr. Vedantham further commented on additional details now available in the NEJM publication that were not part of the original presentation.
"In the published paper, we present more information on the treatment of enrolled patients that enables a reader to gauge the degree to which potential confounding factors could have influenced the study assessments," he said. "Specifically, we have detailed the baseline population characteristics, details of medical and compression therapy, details of endovascular therapy, and follow-up. In addition, the reader can see more data on the secondary study outcomes—in particular, leg pain and swelling, the severity of the postthrombotic syndrome, and QOL. We believe this detail will enable the reader to appreciate the outstanding level of thought and diligence with which the study was designed and performed, enabling greater confidence in its findings."
Dr. Vedantham further suggested that the study will have continued impact, noting, "The ATTRACT trial will influence clinical practice by reducing the routine use of endovascular therapy for acute DVT treatment. The results illustrate that catheter-based intervention focused on the 'open-vein hypothesis' is not the sole answer to eliminating the late effects of DVT, but that with further study, it may form part of the answer to reducing the degree of disability these patients experience. This paper will spur additional work aimed at identifying which patient subgroups (if any) may benefit, enabling a more targeted approach to therapy, and will hopefully also redirect research efforts to better understand both the open vein hypothesis and other biological mechanisms that influence postthrombotic syndrome. Finally, this study’s most enduring legacy may prove to be its impact on promoting collaboration among thrombosis researchers from different medical specialties—this has already resulted in additional National Institutes of Health trial submissions and improved DVT guideline development processes."
Looking to future ATTRACT analysis, Dr. Vedantham commented that ongoing efforts will explore more detailed analyses of the iliofemoral and femoropopliteal subgroup populations, the costs of treatment, patients’ QOL during the treatment period, factors which influenced treatment safety, and correlations between thrombus removal, late venous status (valvular reflux and residual thrombus), postthrombotic syndrome, and QOL.
As a reminder, Endovascular Today is soliciting questions for the ATTRACT investigators. Now that ATTRACT has been published, we will work to have as many questions as possible addressed in a future Endovascular Today feature article. Please send questions to: askATTRACT@bmctoday.com.