Long-term strategies in patients with unprovoked venous thromboembolism

P. Prandoni

doi:10.12687/phleb2372-5-2017

Phlebologie, Inhaltsverzeichnis

Phlebologie 2017; 46(05): 288-291
DOI: 10.12687/phleb2372-5-2017

Ratschow-Medaille 2017

Schattauer GmbH

Long-term strategies in patients with unprovoked venous thromboembolism

Langzeitstrategien bei Patienten mit spontanem venösem Thromboembolismus

P. Prandoni

¹Department of Cardiovascular Sciences, Vascular Medicine Unit, University of Padua, Italy

› Institutsangaben

Abstract

Summary

Once anticoagulation is stopped, the risk of recurrent venous thromboembolism (VTE) over years approaches 40 % of all patients with a first episode of VTE. The risk is twice as high in patients with unprovoked VTE than in those with minor (either transient or persistent) risk factors of thrombosis. Although the latest international guidelines suggest indefinite anticoagulation for most patients with a first episode of unprovoked VTE, strategies that incorporate the assessment of residual vein thrombosis and D-dimer have the potential to identify a substantial proportion of subjects in whom anticoagulation can be safely discontinued. For those patients in whom anticoagulation cannot be discontinued, new opportunities are offered by the availability of low-dose anti-Xa compounds, which have been found to possess an extremely favorable benefit/risk profile.

Zusammenfassung

Nach Absetzen der Antikoagulation beträgt das Rezidivrisiko für venöse Thrombembolien (VTE) über Jahre etwa 40% aller Patienten mit einer ersten VTE-Episode. Das Risiko ist bei Patienten mit spontan aufgetretenen VTE doppelt so hoch wie bei Vorliegen von geringfügigen (passageren oder persistierenden) Risikofaktoren für eine Thrombose. Zwar empfehlen die aktuellen internationalen Richtlinien für die meisten Patienten mit einer erstmaligen, spontanen VTE-Episode eine unbegrenzte Antikoagulation, jedoch bieten Strategien wie u.a. die Beurteilung verbliebener Thrombosereste und die D-Dimer-Bestim-mung die Möglichkeit, einen maßgeblichen Anteil der Patienten zu identifizieren, bei denen die Antikoagulation ohne Risiko beendet werden kann. Für Patienten, bei denen die Antikoagulanzien nicht abgesetzt werden können, eröffnen sich neue Möglichkeiten durch die Verfügbarkeit von niedrig dosierten Faktor-Xa-Hemmern, für die ein extrem günstiges Nutzen-/Risikoprofil nachgewiesen wurde.

Keywords

Venous thromboembolism - deep venous thrombosis - pulmonary embolism - anticoagulation - residual thrombosis - D-dimer - direct oral anticoagulants

Schlüsselwörter

Venöser Thromboembolismus - tiefe Venenthrombose - Lungenembolie - Antikoagulation - residual thrombosis - D-dimer - direkte orale Antikoagulanzien

Volltext

Referenzen

References
1 Prandoni P, Noventa F, Ghirarduzzi A, Pengo V, Bernardi E, Pesavento R. et al. 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 1626 patients. Haematologica 2007; 92: 199-205.
2 Boutitie F, Pinede L, Schulman S, Agnelli G, Raskob G, Julian J. et al. Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants‘ data from seven trials. BMJ 2011; 342: d3036.
3 Couturaud F, Sanchez O, Pernod G, Mismetti P, Jego P, Duhamel E. et al. Six months vs extended oral anticoagulation after a first episode of pulmonary embolism: the PADIS-PE randomized clinical trial. JAMA 2015; 314: 31-40.
4 Lijfering WM, Tait CR, Baglin T, Kyrle PA, Cannegieter SC. et al. Sex difference in the risk of recurrent venous thrombosis: a detailed analysis in four European cohorts. J Thromb Haemost 2015; 13: 1815-1822.
5 Kearon C, Julian JA, Kovacs MJ, Anderson DR, Wells P, Mackinnon B. et al. Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: Results from a randomized trial. Blood 2008; 112: 4432-4436.
6 Segal JB, Brotman DJ, Necochea AJ, Emadi A, Samal L, Wilson LM. et al. Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review. JAMA 30 2009; 1: 2472-2485.
7 Lijfering WM, Middeldorp S, Veeger NJ, Hamulyák K, Prins MH, Büller HR. et al. Risk of recurrent venous thrombosis in homozygous carriers and double heterozygous carriers of factor V Leiden and prothrombin G20210A. Circulation 2010; 121: 1706-1712.
8 Prandoni P, Barbar S, Milan M, Campello E, Spiezia L, Piovella C. et al. Optimal duration of anticoagulation. Provoked versus unprovoked VTE and role of adjunctive thrombophilia and imaging tests. Thromb Haemost 2015; 113: 1210-1215.
9 Palareti G, Legnani C, Cosmi B, Valdré L, Lunghi B, Bernardi F. et al. Predictive value of D-Dimer test for recurrent venous thromboembolism after anticoagulation withdrawal in subjects with a previous idiopathic event and in carriers of congenital thrombophilia. Circulation 2003; 108: 313-318.
10 Palareti G, Legnani C, Cosmi B, Guazzaloca G, Pancani C, Coccheri S. Risk of venous thromboembolism recurrence: high negative predictive value of D-dimer performed after oral anticoagulation is stopped. Thromb Haemost 2002; 87: 7-12.
11 Eichinger S, Minar E, Bialonczyk C, Hirschl M, Quehenberger P, Schneider B. et al. D-dimer levels and risk of recurrent venous thromboembolism. JAMA 2003; 290: 1071-1074.
12 Verhovsek M, Douketis JD, Yi Q, Shrivastava S, Tait RC, Baglin T. et al. Systematic review: D-dimer to predict recurrent disease after stopping anticoagulant therapy for unprovoked venous thromboembolism. Ann Intern Med 2008; 149: 481-90.
13 Bruinstroop E, Klok FA, van de Ree MA, Oosterwijk FL, Huisman MV. Elevated D-dimer levels predict recurrence in patients with idiopathic venous thromboembolism: a meta-analysis. J Thromb Haemost 2009; 7: 611-618.
14 Prandoni P, Lensing AW, Prins MH, Bernardi E, Marchiori A, Bagatella P. et al. Residual venous thrombosis as a predictive factor of recurrent venous thromboembolism. Ann Intern Med 2002; 137: 955-960.
15 Piovella F, Crippa L, Barone M, Viganò D’Angelo S, Serafini S, Galli L. et al. Normalization rates of compression ultrasonography in patients with a first episode of deep vein thrombosis of the lower limbs: association with recurrence and new thrombosis. Haematologica 2002; 87: 515-522.
16 Tan M, Mos IC, Klok FA, Huisman MV. Residual venous thrombosis as predictive factor for recurrent venous thromboembolim in patients with proximal deep vein thrombosis: a sytematic review. Br J Haematol 2011; 153: 168-178.
17 Donadini MP, Ageno W, Antonucci E, Cosmi B, Kovacs MJ, Le Gal G. et al. Prognostic significance of residual venous obstruction in patients with treated unprovoked deep vein thrombosis. A patient-level meta-analysis. Thromb Haemost 2014; 111: 172-179.
18 Prandoni P, Lensing AW, Prins MH, Pesavento R, Piccioli A, Sartori MT. et al. The impact of residual thrombosis on the long-term outcome of patients with deep venous thrombosis treated with conventional anticoagulation. Semin Thromb Hemost 2015; 41: 133-140.
19 Prandoni P, Lensing AW, Prins MH, Villalta S, Harenberg J, Noventa F. Residual vein thrombosis and the risk of subsequent serious complications. Thromb Res 2015; 136: 178-179.
20 Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H. et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest 2016; 149: 315-352.
21 van Es N, Coppens M, Schulman S, Middeldorp S, Büller HR. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood 2014; 124: 1968-1975.
22 The Einstein Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363: 2499-2510.
23 Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D. et al. Extended Use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 2013; 368: 709-718.
24 Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M. et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med 2013; 368: 699-708.
25 Weitz JI, Lensing AWA, Prins MH, Bauersachs R, Beyer Westendorf J, Bounameaux H. et al. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism. N Engl J Med 2017; 376: 1211-1222.
26 Becattini C, Agnelli G, Schenone A, Eichinger S, Bucherini E, Silingardi M. et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med 2012; 366: 1959-1967.
27 Brighton TA, Eikelboom JW, Mann K, Mister R, Gallus A, Ockelford P. et al. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med 2012; 367: 1979-1987.
28 Simes J, Becattini C, Agnelli G, Eikelboom JW, Kirby AC, Mister R. et al. Aspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration. Circulation 2014; 130: 1062-1071.
29 Andreozzi GM, Bignamini AA, Davì G, Palareti G, Matuška J, Holý M. et al. Sulodexide for the prevention of recurrent venous thromboembolism: a multicenter, randomized, double-blind, placebo-controlled trial. Circulation 2015; 132: 1891-1897.
30 Palareti G, Cosmi B, Legnani C, Antonucci E, De Micheli V, Ghirarduzzi A. et al. D-dimer and residual thrombosis to guide the duration of anticoagulation in patients with venous thromboembolism. A management study. Blood 2014; 124: 196-203.
31 Palareti G, Cosmi B, Antonucci E, Legnani C, Erba N, Ghirarduzzi A. et al. Duration of anticoagulation after isolated pulmonary embolism. Eur Respir J 2016; 47: 1429-1435.
32 Prandoni P, Vedovetto V, Ciammaichella M, Bucherini E, Corradini S, Enea I. et al. Residual vein thrombosis and serial D-dimer for the long-term management of patients with deep venous thrombosis. Thromb Res 2017; 154: 35-41.
33 Ageno W, Samperiz A, Caballero R, Dentali F, Di Micco P, Prandoni P. et al. Duration of anticoagulation after venous thromboembolism in real world clinical practice. Thromb Res 2015; 135: 666-672.