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Pharmacomechanical Therapy for Deep-Vein Thrombosis

To the Editor

Regarding the recently published trial by Vedantham et al. (Dec. 7 issue),1 we wish to comment on the results that show an apparent lack of effectiveness of pharmacomechanical catheter-directed thrombolysis in preventing the post-thrombotic syndrome in patients with acute proximal deep-vein thrombosis. Only 58% of the patients had deep-vein thrombosis involving the iliac or common femoral veins, whereas 42% had femoral deep-vein thrombosis, which is associated with a lower risk of the post-thrombotic syndrome.2 In addition, a high percentage of patients (28%) received a venous stent (vs. 5.7% of the patients in the CAVENT [Catheter-Directed Venous Thrombolysis in Acute Iliofemoral Vein Thrombosis] trial3). We wonder whether stent occlusion may have contributed to a higher incidence of the post-thrombotic syndrome in the pharmacomechanical-thrombolysis group than in the control group. Finally, various nonstandardized methods of pharmacomechanical catheter-directed thrombolysis were used, which makes interpretation difficult. Despite all these factors, the incidence of moderate-to-severe post-thrombotic syndrome was substantially lower in the pharmacomechanical-thrombolysis group than in the control group, and there were similar rates of major bleeding events at 24 months in the two groups. Given these issues, we believe that the outcomes of this trial are not generalizable. However, this trial does highlight the need for further studies with careful selection of patients and a more standardized approach.

Sarju Ganatra, M.D.
Ajay Sharma, M.D.
Michael S. Levy, M.D.
Lahey Hospital and Medical Center, Burlington, MA

No potential conflict of interest relevant to this letter was reported.

  1. 1. Vedantham S, Goldhaber SZ, Julian JA, et al. Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis. N Engl J Med 2017;377:22402252.

  2. 2. 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;149:698707.

  3. 3. Enden T, Haig Y, Kløw 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 2012;379:3138.


The authors reply: Patients with femoral deep-vein thrombosis were included in our trial because they also are at high risk for the post-thrombotic syndrome (which occurred in our trial in 44% of the patients with femoral deep-vein thrombosis vs. 50% of those with iliofemoral deep-vein thrombosis).1 Even in patients with iliofemoral deep-vein thrombosis, pharmacomechanical thrombolysis did not prevent the post-thrombotic syndrome (which occurred in 49% of the patients with iliofemoral deep-vein thrombosis in the pharmacomechanical-thrombolysis group and in 51% of those in the control group). However, pharmacomechanical thrombolysis resulted in a lower rate of moderate-to-severe post-thrombotic syndrome and in less severity of the symptoms and signs of the post-thrombotic syndrome than was observed in the control group. These benefits appeared to be confined to patients with iliofemoral deep-vein thrombosis.

The thrombolytic methods used in this trial were standardized and reflected contemporary practice in the United States.2 All the operators were credentialed, and there were rigorous requirements for thrombolytic-drug administration and device use. Per accepted practice, stenting of residual iliac-vein lesions causing a reduction of more than 50% in the vein diameter, a pressure gradient of more than 2 mm Hg, or robust collateral filling was encouraged.3,4 In the absence of a convincingly higher rate of recurrent deep-vein thrombosis in the pharmacomechanical-thrombolysis group than in the control group, it is unlikely that stent thrombosis was an important contributor to the post-thrombotic syndrome. The broad inclusion criteria, contemporary thrombolytic methods, and accommodation of physician expertise that were used in our trial support the generalizability of its results.

Suresh Vedantham, M.D.
Washington University in St. Louis, St. Louis, MO

Samuel Z. Goldhaber, M.D.
Harvard Medical School, Boston, MA

Clive Kearon, M.B., Ph.D.
McMaster University, Hamilton, ON, Canada

Since publication of their article, the authors report no further potential conflict of interest.

  1. 1. 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;149:698707.

  2. 2. 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(4):523530.e3.

  3. 3. Jaff MR, McMurtry MS, Archer SL, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011;123:17881830.

  4. 4. Vedantham S, Sista AK, Klein SJ, et al. Quality improvement guidelines for the treatment of lower-extremity deep vein thrombosis with use of endovascular thrombus removal. J Vasc Interv Radiol 2014;25:13171325.

Source: Massachusetts Medical Society: New England Journal of Medicine: Table of Contents