PDF herunterladen
Thromb Haemost 2019; 119(04): 633-644
DOI: 10.1055/s-0039-1677795
Coagulation and Fibrinolysis
Georg Thieme Verlag KG Stuttgart · New York

Pharmacomechanical Catheter-Directed Thrombolysis in Acute Femoral–Popliteal Deep Vein Thrombosis: Analysis from a Stratified Randomized Trial

Clive Kearon
1   Department of Medicine, McMaster University, Hamilton, Ontario, Canada
,
Chu-Shu Gu
2   Department of Oncology, McMaster University, Hamilton, Ontario, Canada
,
Jim A. Julian
2   Department of Oncology, McMaster University, Hamilton, Ontario, Canada
,
Samuel Z. Goldhaber
3   Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States
,
Anthony J. Comerota
4   Inova Alexandria Health Care, Alexandria, Virginia, United States
,
Heather L. Gornik
5   Department of Medicine, Cleveland Clinic, Cleveland, Ohio, United States
,
Timothy P. Murphy
6   Department of Diagnostic Imaging, Brown University, Providence, Rhode Island, United States
,
Laurence Lewis
7   Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States
,
Susan R. Kahn
8   Department of Medicine, McGill University, Montreal, Quebec, Canada
,
Andrei L. Kindzelski
9   Division of Blood Diseases & Resources, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States
,
Dennis Slater
10   Eastern Connecticut Hematology and Oncology Associates, Norwich, Connecticut, United States
,
Randolph Geary
11   Department of Vascular and Endovascular Surgery, Wake Forest School of Medicine, Wake Forest University, Winston-Salem, North Carolina, United States
,
Ronald Winokur
12   Department of Radiology, Weill Cornell Medicine, New York, New York, United States
,
Kannan Natarajan
13   St. Vincent Hospital, Indianapolis, Indiana, United States
,
Alan Dietzek
14   Department of Surgery, University of Vermont College of Medicine, University of Vermont, Burlington, Vermont, United States
,
Daniel A. Leung
15   Department of Radiology, Christiana Care Health Services, Edgemoor, Delaware, United States
,
Stanley Kim
16   Division of Vascular Surgery, Central DuPage Hospital, Winfield, Illinois, United States
,
Suresh Vedantham
17   Department of Radiology, Washington University in St. Louis, St. Louis, Missouri, United States
› Institutsangaben Funding ATTRACT was supported by grants from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH) for the clinical coordinating centre (U01–088476 to Dr. Suresh Vedantham, Washington University in St. Louis) and data coordinating centre (U01–088118 to Dr. Clive Kearon, McMaster University in Hamilton, Ontario); Washington University's Center for Translational Therapies in Thrombosis which is supported by a grant from NHLBI (U54-HL112303 to Dr. Evan Sadler) and Washington University's Institute of Clinical & Translational Sciences which is supported by a grant from the National Center for the Advancement of Translational Sciences (NCATS) (UL1-TR00044810 to Dr. Bradley Evanoff).
Boston Scientific and Covidien (now Medtronic) provided supplemental funding. Study drug and funding were provided by Genentech (a Roche Company). Compression stockings were donated by BSN Medical. These companies played no role in the study's design, conduct, analysis or reporting.
The study's development and conduct were supported by the Society of Interventional Radiology Foundation. Dr. Kahn is a Tier 1 Canada Research Chair holder and is an investigator of the Canadian Institutes of Health Research-funded CanVECTOR Network. Dr. Kearon is supported by an Investigator Award from the Heart and Stroke Foundation of Canada and the Jack Hirsh Professorship in Thromboembolism. The authors wish to thank the patients who participated, and the entire network of investigators and study staff at the coordinating centres, core laboratories and clinical centres.
Weitere Informationen

Publikationsverlauf

02. November 2018

21. Dezember 2018

Publikationsdatum:
30. Januar 2019 (online)

    Lizenzen und Reprints

Abstract

Background and Objectives The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial reported that pharmacomechanical catheter-directed thrombolysis (PCDT) did not reduce post-thrombotic syndrome (PTS), but reduced moderate-to-severe PTS and the severity of PTS symptoms. In this analysis, we examine the effect of PCDT in patients with femoral–popliteal deep vein thrombosis (DVT) (without involvement of more proximal veins).

Patients and Methods Within the ATTRACT trial, 300 patients had DVT involving the femoral vein without involvement of the common femoral or iliac veins and were randomized to receive PCDT with anticoagulation or anticoagulation alone (no PCDT). Patients were followed for 24 months.

Results From 6 to 24 months, between the PCDT versus no PCDT arms, there was: no difference in any PTS (Villalta scale ≥ 5: risk ratio [RR] = 0.97; 95% confidence interval [CI], 0.75–1.24); moderate-or-severe PTS (Villalta scale ≥ 10: RR = 0.93; 95% CI, 0.57–1.52); severity of PTS scores; or general or disease-specific quality of life (p > 0.5 for all comparisons). From baseline to both 10 and 30 days, there was no difference in improvement of leg pain or swelling between treatment arms. From baseline to 10 days, major bleeding occurred in three versus none (p = 0.06) and any bleeding occurred in eight versus two (p = 0.032) PCDT versus no PCDT patients. Over 24 months, recurrent venous thromboembolism occurred in 16 PCDT and 12 no PCDT patients (p = 0.24).

Conclusion In patients with femoral–popliteal DVT, PCDT did not improve short- or long-term efficacy outcomes, but it increased bleeding. Therefore, PCDT should not be used as initial treatment of femoral–popliteal DVT. (NCT00790335).

Keywords

clinical trial - post-thrombotic syndrome - thrombolytic - treatment - venous thrombosis

Supplementary Material

 

  • References

  • 1 Vedantham S, Goldhaber SZ, Kahn SR. , et al. Rationale and design of the ATTRACT Study: a multicenter randomized trial to evaluate pharmacomechanical catheter-directed thrombolysis for the prevention of postthrombotic syndrome in patients with proximal deep vein thrombosis. Am Heart J 2013; 165 (04) 523-530
    CrossrefPubMedGoogle Scholar
  • 2 Vedantham S, Goldhaber SZ, Julian JA. , et al; ATTRACT Trial Investigators. Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis. N Engl J Med 2017; 377 (23) 2240-2252
    CrossrefPubMedGoogle Scholar
  • 3 Douketis JD, Crowther MA, Foster GA, Ginsberg JS. Does the location of thrombosis determine the risk of disease recurrence in patients with proximal deep vein thrombosis?. Am J Med 2001; 110 (07) 515-519
    CrossrefPubMedGoogle Scholar
  • 4 Kahn SR, Shrier I, Julian JA. , et al. Determinants and time course of the postthrombotic syndrome after acute deep venous thrombosis. Ann Intern Med 2008; 149 (10) 698-707
    Google Scholar
  • 5 Kahn SR, Partsch H, Vedantham S, Prandoni P, Kearon C. ; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of post-thrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardization. J Thromb Haemost 2009; 7 (05) 879-883
    CrossrefPubMedGoogle Scholar
  • 6 Kahn SR. Measurement properties of the Villalta scale to define and classify the severity of the post-thrombotic syndrome. J Thromb Haemost 2009; 7 (05) 884-888
    CrossrefPubMedGoogle Scholar
  • 7 Vasquez MA, Rabe E, McLafferty RB. , et al; American Venous Forum Ad Hoc Outcomes Working Group. Revision of the venous clinical severity score: venous outcomes consensus statement: special communication of the American Venous Forum Ad Hoc Outcomes Working Group. J Vasc Surg 2010; 52 (05) 1387-1396
    CrossrefPubMedGoogle Scholar
  • 8 Marder VJ, Soulen RL, Atichartakarn V. , et al. Quantitative venographic assessment of deep vein thrombosis in the evaluation of streptokinase and heparin therapy. J Lab Clin Med 1977; 89 (05) 1018-1029
    PubMedGoogle Scholar
  • 9 Ware JE, Kosinski MA, Keller S. SF-36 Physical and Mental Measures: A User's Manual. Boston, MA: The Health Institute, New England Medical Centre; 1994
    Google Scholar
  • 10 Lamping DL, Schroter S, Kurz X, Kahn SR, Abenhaim L. Evaluation of outcomes in chronic venous disorders of the leg: development of a scientifically rigorous, patient-reported measure of symptoms and quality of life. J Vasc Surg 2003; 37 (02) 410-419
    CrossrefPubMedGoogle Scholar
  • 11 Wallach JD, Sullivan PG, Trepanowski JF, Sainani KL, Steyerberg EW, Ioannidis JP. Evaluation of evidence of statistical support and corroboration of subgroup claims in randomized clinical trials. JAMA Intern Med 2017; 177 (04) 554-560
    CrossrefPubMedGoogle Scholar
  • 12 Sun X, Briel M, Busse JW. , et al. Credibility of claims of subgroup effects in randomised controlled trials: systematic review. BMJ 2012; 344: e1553
    CrossrefPubMedGoogle Scholar
  • 13 Comerota AJ, Kearon C, Gu CS. , et al. Endovascular thrombus removal for acute iliofemoral deep vein thrombosis: analysis from a Stratified Multicenter Randomized Trial. Circulation; 2018. Published ahead of print December4, 2018. Available at: https://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.118.037425 . Accessed January 10, 2019
    PubMedGoogle Scholar
  • 14 Enden T, Haig Y, Kløw NE. , et al; CaVenT Study Group. 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 2012; 379 (9810): 31-38
    CrossrefPubMedGoogle Scholar
  • 15 Haig Y, Enden T, Grøtta O. , et al; CaVenT Study Group. Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial. Lancet Haematol 2016; 3 (02) e64-e71
    CrossrefPubMedGoogle Scholar