Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis

Suresh Vedantham; Samuel Z. Goldhaber; Jim A. Julian; Susan R. Kahn; Michael R. Jaff; David J. Cohen; Elizabeth Magnuson; Mahmood K. Razavi; Anthony J. Comerota; Heather L. Gornik; Timothy P. Murphy; Lawrence Lewis; James R. Duncan; Patricia Nieters; Mary C. Derfler; Marc Filion; Chu Shu Gu; Stephen Kee; Joseph R Schneider; Nael Saad; Morey Blinder; Stephan Moll; David Sacks; Judith Lin; John Rundback; Mark Garcia; Rahul Razdan; Eric VanderWoude; Vasco Marques; Clive Kearon

doi:10.1056/NEJMoa1615066

Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis

Suresh Vedantham^*, Samuel Z. Goldhaber, Jim A. Julian, Susan R. Kahn, Michael R. Jaff, David J. Cohen, Elizabeth Magnuson, Mahmood K. Razavi, Anthony J. Comerota, Heather L. Gornik, Timothy P. Murphy, Lawrence Lewis, James R. Duncan, Patricia Nieters, Mary C. Derfler, Marc Filion, Chu Shu Gu, Stephen Kee, Joseph R Schneider, Nael SaadMorey Blinder, Stephan Moll, David Sacks, Judith Lin, John Rundback, Mark Garcia, Rahul Razdan, Eric VanderWoude, Vasco Marques, Clive Kearon

^*Corresponding author for this work

Surgery, Vascular Surgery Division

Research output: Contribution to journal › Article › peer-review

598 Scopus citations

Abstract

BACKGROUND The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheterdirected thrombolysis (hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome. METHODS We randomly assigned 692 patients with acute proximal deep-vein thrombosis 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 development of the post-thrombotic syndrome between 6 and 24 months of follow-up. RESULTS Between 6 and 24 months, there was no significant between-group difference in the percentage of patients with the post-thrombotic syndrome (47% in the pharmacomechanical- thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.11; P = 0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P = 0.049), 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 = 0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of patients in the pharmacomechanical-thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P = 0.04). Severity scores for the post-thrombotic syndrome were lower in the pharmacomechanicalthrombolysis group than in the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups. CONCLUSIONS Among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of the post-thrombotic syndrome but did result in a higher risk of major bleeding.

Original language	English (US)
Pages (from-to)	2240-2252
Number of pages	13
Journal	New England Journal of Medicine
Volume	377
Issue number	23
DOIs	https://doi.org/10.1056/NEJMoa1615066
State	Published - Dec 7 2017

Funding

Supported by grants from the National Heart, Lung, and Blood Institute (NHLBI) for the clinical coordinating center (U01-HL088476 to Washington University in St. Louis) and data coordinating center (U01-HL088118 to McMaster University, Hamilton, ON); the Washington University Center for Translational Therapies in Thrombosis, which is supported by a grant from the NHLBI (U54-HL112303); the Washington University Institute of Clinical and Translational Sciences, which is supported by a grant from the National Center for the Advancement of Translational Sciences (UL1-TR00044810); Boston Scientific; Covidien (now Medtronic); Genentech; the Society of Interventional Radiology Foundation; the Canada Research Chairs Program (Tier 1 support to Dr. Kahn); the CanVECTOR Network (funded by Canadian Institutes of Health Research, to Dr. Kahn); the Heart and Stroke Foundation of Canada (Investigator Award to Dr. Kearon); and a Jack Hirsh Professorship in Thrombosis (to Dr. Kearon). BSN Medical donated the compression stockings.

ASJC Scopus subject areas

General Medicine

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10.1056/NEJMoa1615066

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Vedantham, S., Goldhaber, S. Z., Julian, J. A., Kahn, S. R., Jaff, M. R., Cohen, D. J., Magnuson, E., Razavi, M. K., Comerota, A. J., Gornik, H. L., Murphy, T. P., Lewis, L., Duncan, J. R., Nieters, P., Derfler, M. C., Filion, M., Gu, C. S., Kee, S., Schneider, J. R., ... Kearon, C. (2017). Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis. New England Journal of Medicine, 377(23), 2240-2252. https://doi.org/10.1056/NEJMoa1615066

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title = "Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis",

abstract = "BACKGROUND The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheterdirected thrombolysis (hereafter {"}pharmacomechanical thrombolysis{"}) rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome. METHODS We randomly assigned 692 patients with acute proximal deep-vein thrombosis 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 development of the post-thrombotic syndrome between 6 and 24 months of follow-up. RESULTS Between 6 and 24 months, there was no significant between-group difference in the percentage of patients with the post-thrombotic syndrome (47% in the pharmacomechanical- thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.11; P = 0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P = 0.049), 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 = 0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of patients in the pharmacomechanical-thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P = 0.04). Severity scores for the post-thrombotic syndrome were lower in the pharmacomechanicalthrombolysis group than in the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups. CONCLUSIONS Among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of the post-thrombotic syndrome but did result in a higher risk of major bleeding.",

author = "Suresh Vedantham and Goldhaber, {Samuel Z.} and Julian, {Jim A.} and Kahn, {Susan R.} and Jaff, {Michael R.} and Cohen, {David J.} and Elizabeth Magnuson and Razavi, {Mahmood K.} and Comerota, {Anthony J.} and Gornik, {Heather L.} and Murphy, {Timothy P.} and Lawrence Lewis and Duncan, {James R.} and Patricia Nieters and Derfler, {Mary C.} and Marc Filion and Gu, {Chu Shu} and Stephen Kee and Schneider, {Joseph R} and Nael Saad and Morey Blinder and Stephan Moll and David Sacks and Judith Lin and John Rundback and Mark Garcia and Rahul Razdan and Eric VanderWoude and Vasco Marques and Clive Kearon",

year = "2017",

month = dec,

day = "7",

doi = "10.1056/NEJMoa1615066",

language = "English (US)",

volume = "377",

pages = "2240--2252",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

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Vedantham, S, Goldhaber, SZ, Julian, JA, Kahn, SR, Jaff, MR, Cohen, DJ, Magnuson, E, Razavi, MK, Comerota, AJ, Gornik, HL, Murphy, TP, Lewis, L, Duncan, JR, Nieters, P, Derfler, MC, Filion, M, Gu, CS, Kee, S, Schneider, JR, Saad, N, Blinder, M, Moll, S, Sacks, D, Lin, J, Rundback, J, Garcia, M, Razdan, R, VanderWoude, E, Marques, V & Kearon, C 2017, 'Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis', New England Journal of Medicine, vol. 377, no. 23, pp. 2240-2252. https://doi.org/10.1056/NEJMoa1615066

TY - JOUR

T1 - Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis

AU - Vedantham, Suresh

AU - Goldhaber, Samuel Z.

AU - Julian, Jim A.

AU - Kahn, Susan R.

AU - Jaff, Michael R.

AU - Cohen, David J.

AU - Magnuson, Elizabeth

AU - Razavi, Mahmood K.

AU - Comerota, Anthony J.

AU - Gornik, Heather L.

AU - Murphy, Timothy P.

AU - Lewis, Lawrence

AU - Duncan, James R.

AU - Nieters, Patricia

AU - Derfler, Mary C.

AU - Filion, Marc

AU - Gu, Chu Shu

AU - Kee, Stephen

AU - Schneider, Joseph R

AU - Saad, Nael

AU - Blinder, Morey

AU - Moll, Stephan

AU - Sacks, David

AU - Lin, Judith

AU - Rundback, John

AU - Garcia, Mark

AU - Razdan, Rahul

AU - VanderWoude, Eric

AU - Marques, Vasco

AU - Kearon, Clive

PY - 2017/12/7

Y1 - 2017/12/7

N2 - BACKGROUND The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheterdirected thrombolysis (hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome. METHODS We randomly assigned 692 patients with acute proximal deep-vein thrombosis 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 development of the post-thrombotic syndrome between 6 and 24 months of follow-up. RESULTS Between 6 and 24 months, there was no significant between-group difference in the percentage of patients with the post-thrombotic syndrome (47% in the pharmacomechanical- thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.11; P = 0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P = 0.049), 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 = 0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of patients in the pharmacomechanical-thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P = 0.04). Severity scores for the post-thrombotic syndrome were lower in the pharmacomechanicalthrombolysis group than in the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups. CONCLUSIONS Among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of the post-thrombotic syndrome but did result in a higher risk of major bleeding.

AB - BACKGROUND The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheterdirected thrombolysis (hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome. METHODS We randomly assigned 692 patients with acute proximal deep-vein thrombosis 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 development of the post-thrombotic syndrome between 6 and 24 months of follow-up. RESULTS Between 6 and 24 months, there was no significant between-group difference in the percentage of patients with the post-thrombotic syndrome (47% in the pharmacomechanical- thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.11; P = 0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P = 0.049), 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 = 0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of patients in the pharmacomechanical-thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P = 0.04). Severity scores for the post-thrombotic syndrome were lower in the pharmacomechanicalthrombolysis group than in the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups. CONCLUSIONS Among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of the post-thrombotic syndrome but did result in a higher risk of major bleeding.

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Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis

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