A randomised controlled trial of extended anticoagulation treatment versus standard treatment for the prevention of recurrent venous thromboembolism (VTE) and post-thrombotic syndrome in patients being treated for a first episode of unprovoked VTE (the ExACT study).

Szczegóły
Abstrakt

Tytuł:: A randomised controlled trial of extended anticoagulation treatment versus standard treatment for the prevention of recurrent venous thromboembolism (VTE) and post-thrombotic syndrome in patients being treated for a first episode of unprovoked VTE (the ExACT study).
Autorzy:: Bradbury C; School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
Fletcher K; Institute of Applied Health Research, The University of Birmingham, Birmingham, UK.
Sun Y; Institute of Applied Health Research, The University of Birmingham, Birmingham, UK.
Heneghan C; Nuffield Department of Primary Care Health Sciences, Medical Sciences Division, University of Oxford, Oxford, UK.
Gardiner C; Haemostasis Research Unit (HRU), Department of Haematology, University College London, London, UK.
Roalfe A; Nuffield Department of Primary Care Health Sciences, Medical Sciences Division, University of Oxford, Oxford, UK.
Hardy P; Institute of Applied Health Research, The University of Birmingham, Birmingham, UK.
McCahon D; Centre for Academic Primary Care, Bristol Medical School, University of Bristol, Bristol, UK.
Heritage G; Institute of Applied Health Research, The University of Birmingham, Birmingham, UK.
Shackleford H; Institute of Applied Health Research, The University of Birmingham, Birmingham, UK.
Hobbs FR; Nuffield Department of Primary Care Health Sciences, Medical Sciences Division, University of Oxford, Oxford, UK.
Fitzmaurice D; Unit of Academic Primary Care, Warwick Medical School, University of Warwick, Coventry, UK.
Źródło:: British journal of haematology [Br J Haematol] 2020 Mar; Vol. 188 (6), pp. 962-975. Date of Electronic Publication: 2019 Nov 12.
Typ publikacji:: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: Oxford : Wiley-Blackwell
Original Publication: Oxford : Blackwell Scientific Publications
MeSH Terms:: Anticoagulants/*therapeutic use
Venous Thromboembolism/*drug therapy
Aged ; Anticoagulants/pharmacology ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Venous Thromboembolism/prevention & control
References:: Agnelli, G., Prandoni, P., Santamaria, M.G., Bagatella, P., Iorio, A., Bazzan, M., Moia, M., Guazzaloca, G., Bertoldi, A., Tomasi, C. & Scannapieco, G. (2001) Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. Warfarin Optimal Duration Italian Trial Investigators. The New England Journal of Medicine, 345, 165-169.
Agnelli, G., Prandoni, P., Becattini, C., Silingardi, M., Taliani, M.R., Miccio, M., Imberti, D., Poggio, R., Ageno, W., Pogliani, E. & Porro, F. (2003) Extended oral anticoagulant therapy after a first episode of pulmonary embolism. Annals of Internal Medicine, 139, 19-25.
Agnelli, G., Buller, H.R., Cohen, A., Curto, M., Gallus, A.S., Johnson, M., Porcari, A., Raskob, G.E. & Weitz, J.I. (2013) Apixaban for extended treatment of venous thromboembolism. The New England Journal of Medicine, 368, 699-708.
Baglin, T., Luddington, R., Brown, K. & Baglin, C. (2003) Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet, 362, 523-526.
Baglin, T., Douketis, J., Tosetto, A., Marcucci, M., Cushman, M., Kyrle, P., Palareti, G., Poli, D., Tait, R.C. & Iorio, A. (2010) Does the clinical presentation and extent of venous thrombosis predict likelihood and type of recurrence? A patient-level meta-analysis. Journal of Thrombosis and Haemostasis, 8, 2436-2442.
Bauersachs, R., Berkowitz, S.D., Brenner, B., Buller, H.R., Decousus, H., Gallus, A.S., Lensing, A.W., Misselwitz, F., Prins, M.H., Raskob, G.E., Segers, A., Verhamme, P., Wells, P., Agnelli, G., Bounameaux, H., Cohen, A., Davidson, B.L., Piovella, F. & Schellong, S. (2010) Oral rivaroxaban for symptomatic venous thromboembolism. The New England Journal of Medicine, 363, 2499-2510.
Becattini, C., Agnelli, G., Schenone, A., Eichinger, S., Bucherini, E., Silingardi, M., Bianchi, M., Moia, M., Ageno, W., Vandelli, M.R. & Grandone, E. (2012) Aspirin for preventing the recurrence of venous thromboembolism. The New England Journal of Medicine, 366, 1959-1967.
Bell, E.J., Lutsey, P.L., Basu, S., Cushman, M., Heckbert, S.R., Lloyd-Jones, D.M. & Folsom, A.R. (2016) Lifetime risk of venous thromboembolism in two cohort studies. The American Journal of Medicine, 129, 339.e19-339.e26.
Brighton, T.A., Eikelboom, J.W., Mann, K., Mister, R., Gallus, A., Ockelford, P., Gibbs, H., Hague, W., Xavier, D., Diaz, R. & Kirby, A. (2012) Low-dose aspirin for preventing recurrent venous thromboembolism. The New England Journal of Medicine, 367, 1979-1987.
Broderick, C., Armon, M.P. & Watson L. (2016) Thrombolysis for acute deep vein thrombosis. Cochrane Database Systamatic Review, 2016, CD002783.
Campbell, I.A., Bentley, D.P., Prescott, R.J., Routledge, P.A., Shetty, H.G. & Williamson, I.J. (2007) Anticoagulation for three versus six months in patients with deep vein thrombosis or pulmonary embolism, or both: randomised trial. BMJ, 334, 674.
Cohen, A.T., Agnelli, G., Anderson, F.A., Arcelus, J.I., Bergqvist, D., Brecht, J.G., Greer, I.A., Heit, J.A., Hutchinson, J.L., Kakkar, A.K. & Mottier, D. (2007) Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thrombosis and Haemostasis, 98, 756-764.
van Dongen, C.J., Prandoni, P., Frulla, M., Holder, R., Lester, W., Rose, P., Hobbs, F.R. & Fitzmaurice, D. (2005) Relation between quality of anticoagulant treatment and the development of the postthrombotic syndrome. Journal of Thrombosis and Haemostasis, 3, 939-942.
Douketis, J.D., Gu, C.S., Schulman, S., Ghirarduzzi, A., Pengo, V. & Prandoni, P. (2007) The risk for fatal pulmonary embolism after discontinuing anticoagulant therapy for venous thromboembolism. Annals of Internal Medicine, 147, 766-774.
Haig, Y., Enden, T., Grotta, O., Kløw, N.E., Slagsvold, C.E., Ghanima, W., Sandvik, L., Hafsahl, G., Holme, P.A., Holmen, L.O. & Njaaastad, A.M. (2016) Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial. The Lancet Haematology, 3, e64-71.
Kahn, S.R. (2009) Measurement properties of the Villalta scale to define and classify the severity of the post-thrombotic syndrome. Journal of Thrombosis and Haemostasis, 7, 884-888.
Kahn, S.R. (2016) The post-thrombotic syndrome. American Society of Hematology Education Program, 2016, 413-418.
Kahn, S.R., Lamping, D.L., Ducruet, T., Arsenault, L., Miron, M.J., Roussin, A., Desmarais, S., Joyal, F., Kassis, J., Solymoss, S. & Desjardins, L. (2006) VEINES-QOL/Sym questionnaire was a reliable and valid disease-specific quality of life measure for deep venous thrombosis. Journal of Clinical Epidemiology, 59, 1049-1056.
Kahn, S.R., Shbaklo, H., Lamping, D.L., Holcroft, C.A., Shrier, I., Miron, M.J., Roussin, A., Desmarais, S., Joyal, F., Kassis, J. & Solymoss, S. (2008) Determinants of health-related quality of life during the 2 years following deep vein thrombosis. Journal of Thrombosis and Haemostasis, 6, 1105-1112.
Kearon, C. & Akl, E.A. (2014) Duration of anticoagulant therapy for deep vein thrombosis and pulmonary embolism. Blood, 123, 1794-1801.
Kearon, C., Gent, M., Hirsh, J., Weitz, J., Kovacs, M.J., Anderson, D.R., Turpie, A.G., Green, D., Ginsberg, J.S., Wells, P. & MacKinnon, B. (1999) A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. The New England Journal of Medicine, 340, 901-907.
Kearon, C., Spencer, F.A., O'Keeffe, D., Parpia, S., Schulman, S., Baglin, T., Stevens, S.M., Kaatz, S., Bauer, K.A., Douketis, J.D. & Lentz, S.R. (2015) D-dimer testing to select patients with a first unprovoked venous thromboembolism who can stop anticoagulant therapy: a cohort study. Annals of Internal Medicine, 162, 27-34.
Kearon, C., Akl, E.A., Ornelas, J., Blaivas, A., Jimenez, D., Bounameaux, H., Huisman, M., King, C.S., Morris, T.A., Sood, N. & Stevens, S.M. (2016) Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest, 149, 315-352.
Kearon, C., Parpia, S., Spencer, F.A., Schulman, S., Stevens, S.M., Shah, V., Bauer, K.A., Douketis, J.D., Lentz, S.R., Kessler, C.M. & Connors, J.M. (2019) Long term risk of recurrence in patients with a first unprovoked venous thromboembolism managed according to D-dimer results; a cohort study. Journal of Thrombosis and Haemostasis, 17, 1144-1152.
Keeling, D., Baglin, T., Tait, C., Watson, H., Perry, D., Baglin, C., Kitchen, S. & Makris, M. (2011) British Committee for Standards in Haematology. Guidelines on oral anticoagulation with warfarin - fourth edition. British Journal of Haematology, 154, 311-324.
Martinez, C., Cohen, A.T., Bamber, L. & Rietbrock, S. (2014) Epidemiology of first and recurrent venous thromboembolism: a population-based cohort study in patients without active cancer. Thrombosis and Haemostasis, 112, 255-263.
NICE CG 144. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing, 2012. Available at https://www.nice.org.uk/Guidance/cg144 (Accessed March 2019).
Noble, S., Lewis, R., Whithers, J., Lewis, S. & Bennett, P. (2014) Long-term psychological consequences of symptomatic pulmonary embolism: a qualitative study. British Medical Journal Open, 4, e004561.
Nordstrom, B.L., Evans, M.A., Murphy, B.R., Nutescu, E.A., Schein, J.R. & Bookhart, B.K. (2015) Risk of recurrent venous thromboembolism among deep vein thrombosis and pulmonary embolism patients treated with warfarin. Current Medical Research and Opinion, 31, 439-447.
Palareti, G., Legani, C., Guazzaloca, G., Cosmi, B., Pancani, C. & Coccheri, S. (2002) Risk of venous thromboembolism recurrence: high negative predictive value of D-dimer performed after oral anticoagulation is stopped. Thrombosis and Haemostasis, 87, 7-12.
Palareti, G., Cosmi, B. & Legnani, C. (2014) D-dimer to guide the duration of anticoagulation in patients with venous thromboembolism: a management study. Blood, 124, 196-203.
Prandoni, P., Noventa, F., Ghirarduzzi, A., Pengo, V., Bernardi, E., Pesavento, R., Iotti, M., Tormene, D., Simioni, P. & Pagnan, A. (2007) The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica, 92, 199-205.
Roach, R.E., Lijfering, W.M., Tait, R.C., Baglin, T., Kyrle, P.A., Cannegieter, S.C. & Rosendaal, F.R. (2015) Sex difference in the risk of recurrent venous thrombosis: a detailed analysis in four European cohorts. Journal of Thrombosis and Haemostasis, 13, 1815-1822.
Rodger, M.A., Kahn, S.R., Wells, P.S., Chagnon, I., Le Gal, G., Solymoss, S., Crowther, M., Perrier, A., White, R., Vickars, L., Ramsay, T., Betancourt, M.T. & Kovacs, M.J. (2008) Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ: Canadian Medical Association Journal = Journal de l'Association medicale Canadienne, 179, 417-426.
Rodger, M.A., Le Gal, G., Anderson, D.R., Schmidt, J., Pernod, G., Kahn, S.R., Righini, M., Mismetti, P., Kearon, C., Meyer, G., Elias, A., Ramsay, T., Ortel, T.L., Huisman, M.V., Kovacs, M.J. & REVERSE II Study Investigators (2017) Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study. BMJ (Clinical research ed.), 356, j1065. https://doi.org/10.1136/bmj.j1065.
Romualdi, E., Donadini, M.P. & Ageno, W. (2011) Oral rivaroxaban after symptomatic venous thromboembolism: the continued treatment study (EINSTEIN-extension study). Expert Review of Cardiovascular Therapy, 9, 841-844.
Schulman, S., Lindmarker, P., Holmström, M., Lärfars, G., Carlsson, A., Nicol, P., Svensson, E., Ljungberg, B., Viering, S., Nordlander, S., Leijd, B., Jahed, K., Hjorth, M., Linder, O. & Beckman, M. (2006) Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months. Journal of Thrombosis and Haemostasis, 4, 734-742.
Schulman, S., Kearon, C., Kakkar, A.K., Schellong, S., Eriksson, H., Baanstra, D., Kvamme, A.M., Friedman, J., Mismetti, P.,Goldhaber, S.Z., RE-MEDY Trial Investigators, & RE-SONATE Trial Investigators (2013) Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. The New England Journal of Medicine, 368, 709-718.
Sterne, J.A., Bodalia, P.N., Bryden, P.A., Davies, P.A., López-López, J.A., Okoli, G.N., Thom, H.H., Caldwell, D.M., Dias, S., Eaton, D. & Higgins, J.P. (2017) Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis. Health Technology Assessment (Winchester, England), 21, 1-386.
Subbiah, R., Aggarwal, V., Zhao, H., Kolluri, R., Chatterjee, S. & Bashir, R. (2016) Effect of compression stockings on post thrombotic syndrome in patients with deep vein thrombosis: a meta-analysis of randomised controlled trials. The Lancet Haematology., 3, e293-300.
Tosetto, A., Iorio, A., Marcucci, M., Baglin, T., Cushman, M., Eichinger, S., Palareti, G., Poli, D., Tait, R.C. & Douketis, J. (2012) Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH). Journal of Thrombosis and Haemostasis, 10, 1019-1025.
Tullett, J., Murray, E., Nichols, L., et al. (2013) Trial Protocol: a randomised controlled trial of extended anticoagulation treatment versus routine anticoagulation treatment for the prevention of recurrent VTE and post thrombotic syndrome in patients being treated for a first episode of unprovoked VTE (The ExACT Study). BMC Cardiovascular Disorders, 13, 16.
Vedantham, S., Goldhaber, S.Z., Julian, J.A., Kahn, S.R., Jaff, M.R., Cohen, D.J., Magnuson, E. & Razavi, M.K. (2017) Comerota AJ, Gornik HL, Murphy TP, for the ATTRACT Trial Investigators. Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis. New England Journal of Medicine, 377, 2240-2252.
Verhovsek, M., Douketis, J.D., Yi, Q., Shrivastava, S., Tait, R.C., Baglin, T., Poli, D. & Lim, W. (2008) Systematic review: D-dimer to predict recurrent disease after stopping anticoagulant therapy for unprovoked venous thromboembolism. Annals of Internal Medicine., 149, w94.
Weitz, J.I., Lensing, A.W.A., Prins, M.H., Bauersachs, R., Beyer-Westendorf, J., Bounameaux, H., Brighton, T.A., Cohen, A.T., Davidson, B.L., Decousus, H. & Freitas, M.C. (2017) Rivaroxaban or aspirin for extended treatment of venous thromboembolism. The New England Journal of Medicine, 376, 1211-1222.
Wells, P.S., Prins, M.H., Levitan, B., Beyer-Westendorf, J., Brighton, T.A., Bounameaux, H., Cohen, A.T., Davidson, B.L., Prandoni, P., Raskob, G.E. & Yuan, Z. (2016) Long-term anticoagulation with rivaroxaban for preventing recurrent VTE: a benefit-risk analysis of EINSTEIN-extension. Chest, 150, 1059.
Wilbur, J. & Shian, B. (2017) Deep venous thrombosis and pulmonary embolism: current therapy. American Family Physician, 95, 295-302.
Grant Information:: International Programme Grants for Applied Research; International NIHR School for Primary Care Research; International NIHR Collaboration for Leadership in Health Research and Care; International Diagnostics Co-operative; International NIHR Oxford Medtrch; RP-PG-0608-10073 International National Institute for Health Research; International Oxford University Hospitals NHS Foundation Trust; IS-SPC-0514-10043 United Kingdom DH_ Department of Health; International NIHR Oxford Biomedical Research Centre; International Department of Health [UK]; G9900264 United Kingdom MRC_ Medical Research Council
Contributed Indexing:: Keywords: D-dimer; anticoagulation; post-thrombotic syndrome; thrombosis (venous); warfarin
Substance Nomenclature:: 0 (Anticoagulants)
Entry Date(s):: Date Created: 20191113 Date Completed: 20201113 Latest Revision: 20210304
Update Code:: 20240105
DOI:: 10.1111/bjh.16275
PMID:: 31713863
: Czasopismo naukowe

Full Text Finder

Venous thromboembolism (VTE) is prevalent and impactful, with a risk of death, morbidity and recurrence. Post-thrombotic syndrome (PTS) is a common consequence and associated with impaired quality of life (QoL). The ExACT study was a non-blinded, prospective, multicentred randomised controlled trial comparing extended versus limited duration anticoagulation following a first unprovoked VTE (proximal deep vein thrombosis or pulmonary embolism). Adults were eligible if they had completed ≥3 months anticoagulation (remaining anticoagulated). The primary outcome was time to first recurrent VTE from randomisation. The secondary outcomes included PTS severity, bleeding, QoL and D-dimers. Two-hundred and eighty-one patients were recruited, randomised and followed up for 24 months (mean age 63, male:female 2:1). There was a significant reduction in recurrent VTE for patients receiving extended anticoagulation [2·75 vs. 13·54 events/100 patient years, adjusted hazard ratio (aHR) 0·20 (95% confidence interval (CI): 0·09 to 0·46, P < 0·001)] with a non-significant increase in major bleeding [3·54 vs. 1·18 events/100 patient years, aHR 2·99 (95% CI: 0·81-11·05, P = 0·10)]. Outcomes of PTS and QoL were no different between groups. D-dimer results (on anticoagulation) did not predict VTE recurrence. In conclusion, extended anticoagulation reduced VTE recurrence but did not reduce PTS or improve QoL and was associated with a non-significant increase in bleeding. Results also suggest very limited clinical utility of D-dimer testing on anticoagulated patients.
(© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Informacja