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Review

Pharmacological management of pulmonary embolism

, , &
Pages 79-93 | Received 04 Sep 2016, Accepted 30 Nov 2016, Published online: 20 Dec 2016

References

  • Blondon M, Bounameaux H. Secondary prevention of venous thromboembolism: one regimen may not fit all. Circulation. 2015 Nov 17;132(20):1856–1859.
  • Girard P, Sanchez O, Leroyer C, et al. Deep venous thrombosis in patients with acute pulmonary embolism: prevalence, risk factors, and clinical significance. Chest. 2005 Sep;128(3):1593–1600.
  • Sanchez O, Trinquart L, Caille V, et al. Prognostic factors for pulmonary embolism: the prep study, a prospective multicenter cohort study. Am J Respir Crit Care Med. 2010 Jan 15;181(2):168–173.
  • Aujesky D, Obrosky DS, Stone RA, et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med. 2005 Oct 15;172(8):1041–1046.
  • Kearon C. Natural history of venous thromboembolism. Circulation. 2003 Jun 17;107(23 Suppl 1):I22–30.
  • Cohen AT, Agnelli G, Anderson FA, et al. Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost. 2007 Oct;98(4):756–764.
  • Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics–2011 update: a report from the American Heart Association. Circulation. 2011 Feb 1;123(4):e18–e209.
  • Anderson FA Jr., Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med. 1991 May;151(5):933–938.
  • Oger E. Incidence of venous thromboembolism: a community-based study in Western France. EPI-GETBP study group. groupe d’etude de la thrombose de bretagne occidentale. Thromb Haemost. 2000 May;83(5):657–660.
  • Sevestre MA, Quashie C, Genty C, et al. Clinical presentation and mortality in pulmonary embolism: the Optimev study. J Mal Vasc. 2010 Jul;35(4):242–249.
  • Pesavento R, Prandoni P. Prevention and treatment of the post-thrombotic syndrome and of the chronic thromboembolic pulmonary hypertension. Expert Rev Cardiovasc Ther. 2015 Feb;13(2):193–207.
  • Konstantinides SV, Torbicki A, Agnelli G, et al. ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J . 2014 Nov 14;35(43):3033–69, 69a-69k.
  • Marti C, John G, Konstantinides S, et al. Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis. Eur Heart J. 2015 Mar 7;36(10):605–614.
  • Aujesky D, Roy PM, Verschuren F, et al. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial. Lancet. 2011 Jul 2;378(9785):41–48.
  • Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial. Lancet. 1960 Jun 18;1(7138):1309–1312.
  • Brandjes DP, Heijboer H, Buller HR, et al. Acenocoumarol and heparin compared with acenocoumarol alone in the initial treatment of proximal-vein thrombosis. N Engl J Med. 1992 Nov 19;327(21):1485–1489.
  • Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016 Feb;149(2):315–352.
  • Zondag W, Kooiman J, Klok FA, et al. Outpatient versus inpatient treatment in patients with pulmonary embolism: a meta-analysis. Eur Respir J. 2013 Jul;42(1):134–144.
  • Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: american college of chest physicians evidence-based clinical practice guidelines. Chest. 2012 Feb;141((2Suppl)):e419S–94S.
  • Quinlan DJ, McQuillan A, Eikelboom JW. Low-molecular-weight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism: a meta-analysis of randomized, controlled trials. Ann Intern Med. 2004 Feb 3;140(3):175–183.
  • Martel N, Lee J, Wells PS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood. 2005 Oct 15;106(8):2710–2715.
  • Warkentin TE, Sheppard JA, Horsewood P, et al. Impact of the patient population on the risk for heparin-induced thrombocytopenia. Blood. 2000 Sep 1;96(5):1703–1708.
  • Girolami B, Prandoni P, Stefani PM, et al. The incidence of heparin-induced thrombocytopenia in hospitalized medical patients treated with subcutaneous unfractionated heparin: a prospective cohort study. Blood. 2003 Apr 15;101(8):2955–2959.
  • Kearon C, Ginsberg JS, Julian JA, et al. Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism. Jama. 2006 Aug 23;296(8):935–942.
  • Erkens PM, Prins MH. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database Syst Rev. 2010;9:CD001100.
  • Lee AY, Levine MN, Baker RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10;349(2):146–153.
  • Lee AY, Kamphuisen PW, Meyer G, et al. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: a randomized clinical trial. Jama. 2015 Aug 18;314(7):677–686.
  • Ha NB, Regal RE. Anticoagulation in patients with cirrhosis: caught between a rock-liver and a hard place. Ann Pharmacother. 2016 May;50(5):402–409.
  • Kang M, Alahmadi M, Sawh S, et al. Fondaparinux for the treatment of suspected heparin-induced thrombocytopenia: a propensity score-matched study. Blood. 2015 Feb 5;125(6):924–929.
  • Buller HR, Davidson BL, Decousus H, et al. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med. 2003 Oct 30;349(18):1695–1702.
  • Buller HR, Davidson BL, Decousus H, et al. Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial. Ann Intern Med. 2004 Jun 1;140(11):867–873.
  • Erkens PM, Ten Cate H, Buller HR, et al. Benchmark for time in therapeutic range in venous thromboembolism: a systematic review and meta-analysis. Plos One. 2012;7(9):e42269.
  • Investigators E-P, Buller HR, Prins MH, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287–1297.
  • Gouin B, Blondon M, Jimenez D, et al. Clinical prognosis of non-massive central and non-central pulmonary embolism: a registry-based study. Chest. 2016 Nov 19. pii: S0012-3692(16)62358-9. doi: 10.1016/j.chest.2016.10.056. [Epub ahead of print]
  • Kearon C, Gent M, Hirsh J, et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med. 1999 Mar 25;340(12):901–907.
  • Ruiz-Gimenez N, Suarez C, Gonzalez R, et al. Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry. Thromb Haemost. 2008 Jul;100(1):26–31.
  • Carrier M, Le Gal G, Wells PS, et al. Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann Intern Med. 2010 May 4;152(9):578–589.
  • Veeger NJ, Piersma-Wichers M, Tijssen JG, et al. Individual time within target range in patients treated with vitamin K antagonists: main determinant of quality of anticoagulation and predictor of clinical outcome. A retrospective study of 2300 consecutive patients with venous thromboembolism. Br J Haematol. 2005 Feb;128(4):513–519.
  • Kimmel SE, French B, Kasner SE, et al. A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med. 2013 Dec 12;369(24):2283–2293.
  • Pirmohamed M, Burnside G, Eriksson N, et al. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med. 2013 Dec 12;369(24):2294–2303.
  • Kimmel SE. Warfarin pharmacogenomics: current best evidence. J Thromb Haemost. 2015 Jun;13(Suppl 1):S266–71.
  • Fontana P, Robert-Ebadi H, Bounameaux H, et al. Direct oral anticoagulants: a guide for daily practice. Swiss Med Wkly. 2016;146:w14286.
  • Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009 Dec 10;361(24):2342–2352.
  • Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29;369(9):799–808.
  • Hokusai VTEI, Buller HR, Decousus H, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013 Oct 10;369(15):1406–1415.
  • Van Es N, Coppens M, Schulman S, et al. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood. 2014 Sep 18;124(12):1968–1975.
  • Cohen AT, Hamilton M, Mitchell SA, et al. Comparison of the novel oral anticoagulants apixaban, dabigatran, edoxaban, and rivaroxaban in the initial and long-term treatment and prevention of venous thromboembolism: systematic review and network meta-analysis. Plos One. 2015;10(12):e0144856.
  • Ageno W, Mantovani LG, Haas S, et al. Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study. Lancet Haematol. 2016 Jan;3(1):e12–21.
  • Van Gogh I, Buller HR, Cohen AT, et al. Idraparinux versus standard therapy for venous thromboembolic disease. N Engl J Med. 2007 Sep 13;357(11):1094–1104.
  • Raccah BH, Perlman A, Danenberg HD, et al. Major bleeding and hemorrhagic stroke with direct oral anticoagulants in patients with renal failure: systematic review and meta-analysis of randomized trials. Chest. 2016 Jun;149(6):1516–1524.
  • Heidbuchel H, Verhamme P, Alings M, et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013 May;15(5):625–651.
  • Reilly PA, Lehr T, Haertter S, et al. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol. 2014 Feb 4;63(4):321–328.
  • Upreti VV, Wang J, Barrett YC, et al. Effect of extremes of body weight on the pharmacokinetics, pharmacodynamics, safety and tolerability of apixaban in healthy subjects. Br J Clin Pharmacol. 2013 Dec;76(6):908–916.
  • Martin K, Beyer-Westendorf J, Davidson BL, et al. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost. 2016 Jun;14(6):1308–1313.
  • Chai-Adisaksopha C, Hillis C, Isayama T, et al. Mortality outcomes in patients receiving direct oral anticoagulants: a systematic review and meta-analysis of randomized controlled trials. J Thromb Haemost. 2015 Nov;13(11):2012–2020.
  • Dalla-Volta S, Palla A, Santolicandro A, et al. PAIMS 2: alteplase combined with heparin versus heparin in the treatment of acute pulmonary embolism. Plasminogen activator Italian multicenter study 2. J Am Coll Cardiol. 1992 Sep;20(3):520–526.
  • Takahashi H, Okada K, Matsumori M, et al. Aggressive surgical treatment of acute pulmonary embolism with circulatory collapse. Ann Thorac Surg. 2012 Sep;94(3):785–791.
  • Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402–1411.
  • Schulman S, Granqvist S, Holmstrom M, et al. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. The duration of anticoagulation trial study group. N Engl J Med. 1997 Feb 6;336(6):393–398.
  • Prandoni P, Noventa F, Ghirarduzzi A, 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 1,626 patients. Haematologica. 2007 Feb;92(2):199–205.
  • McRae S, Tran H, Schulman S, et al. Effect of patient’s sex on risk of recurrent venous thromboembolism: a meta-analysis. Lancet. 2006 Jul 29;368(9533):371–378.
  • Christiansen SC, Lijfering WM, Helmerhorst FM, et al. Sex difference in risk of recurrent venous thrombosis and the risk profile for a second event. J Thromb Haemost. 2010 Oct;8(10):2159–2168.
  • Ho WK, Hankey GJ, Quinlan DJ, et al. Risk of recurrent venous thromboembolism in patients with common thrombophilia: a systematic review. Arch Intern Med. 2006 Apr 10;166(7):729–736.
  • Eichinger S, Hron G, Bialonczyk C, et al. Overweight, obesity, and the risk of recurrent venous thromboembolism. Arch Intern Med. 2008 Aug 11;168(15):1678–1683.
  • Couturaud F, Sanchez O, Pernod G, et al. Six months vs extended oral anticoagulation after a first episode of pulmonary embolism: the PADIS-PE randomized clinical trial. Jama. 2015 Jul 7;314(1):31–40.
  • Eichinger S, Heinze G, Jandeck LM, et al. Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model. Circulation. 2010 Apr 13;121(14):1630–1636.
  • Farraj RS. Anticoagulation period in idiopathic venous thromboembolism. How long is enough? Saudi Med J. 2004 Jul;25(7):848–851.
  • Ridker PM, Goldhaber SZ, Danielson E, et al. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med. 2003 Apr 10;348(15):1425–1434.
  • Kearon C, Ginsberg JS, Kovacs MJ, et al. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med. 2003 Aug 14;349(7):631–639.
  • Linkins LA, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Ann Intern Med. 2003 Dec 2;139(11):893–900.
  • O’Brien EC, Simon DN, Thomas LE, et al. The ORBIT bleeding score: a simple bedside score to assess bleeding risk in atrial fibrillation. Eur Heart J. 2015 Dec 7;36(46):3258–3264.
  • Investigators E, Bauersachs R, Berkowitz SD, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010 Dec 23;363(26):2499–2510.
  • Wells PS, Prins MH, Levitan B, et al. Long-term anticoagulation with rivaroxaban for preventing recurrent VTE: a benefit-risk analysis of EINSTEIN EXTENSION. Chest. 2016 Nov;150(5):1059–1068.
  • Weitz JI, Bauersachs R, Beyer-Westendorf J, et al. Two doses of rivaroxaban versus aspirin for prevention of recurrent venous thromboembolism. Rationale for and design of the EINSTEIN CHOICE study. Thromb Haemost. 2015 Aug 31;114(3):645–650.
  • Agnelli G, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):699–708.
  • Schulman S, Kearon C, Kakkar AK, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):709–718.
  • Raskob G, Ageno W, Cohen AT, et al. Extended duration of anticoagulation with edoxaban in patients with venous thromboembolism: a post-hoc analysis of the Hokusai-VTE study. Lancet Haematol. 2016 May;3(5):e228–36.
  • Undas A, Brummel-Ziedins K, Mann KG. Why does aspirin decrease the risk of venous thromboembolism? On old and novel antithrombotic effects of acetyl salicylic acid. J Thromb Haemost. 2014 Nov;12(11):1776–1787.
  • Becattini C, Agnelli G, Schenone A, et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med. 2012 May 24;366(21):1959–1967.
  • Brighton TA, Eikelboom JW, Mann K, et al. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med. 2012 Nov 22;367(21):1979–1987.
  • Simes J, Becattini C, Agnelli G, et al. Aspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration. Circulation. 2014 Sep 23;130(13):1062–1071.
  • Andreozzi GM, Bignamini AA, Davi G, et al. Sulodexide for the prevention of recurrent venous thromboembolism: the sulodexide in secondary prevention of recurrent deep vein Thrombosis (SURVET) study: a multicenter, randomized, double-blind, placebo-controlled trial. Circulation. 2015 Nov 17;132(20):1891–1897.
  • Smith NL, Harrington LB, Blondon M, et al. The association of statin therapy with the risk of recurrent venous thrombosis. J Thromb Haemost. 2016 Jul;14(7):1384–1392.
  • Blondon M, Casini A, Hoppe KK, et al. Risks of venous thromboembolism after cesarean sections: a meta-analysis. Chest. 2016 Sep;150(3):572–596.
  • Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. Arch Intern Med. 2000 Jan 24;160(2):191–196.
  • Cohen H, Arachchillage DR, Middeldorp S, et al. Management of direct oral anticoagulants in women of childbearing potential: guidance from the SSC of the ISTH. J Thromb Haemost. 2016 Aug;14(8):1673–1676.
  • Beyer-Westendorf J, Michalski F, Tittl L, et al. Pregnancy outcome in patients exposed to direct oral anticoagulants - and the challenge of event reporting. Thromb Haemost. 2016 Sep 27;116(4):651–658.
  • Elsaigh E, Thachil J, Nash MJ, et al. The use of fondaparinux in pregnancy. Br J Haematol. 2015 Mar;168(5):762–764.
  • Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: antithrombotic therapy and prevention of thrombosis, 9th ed: american college of chest physicians evidence-based clinical practice guidelines. Chest. 2012 Feb;141(2Suppl):e691S–736S.
  • Romualdi E, Dentali F, Squizzato A, et al. Anticoagulant therapy for venous thromboembolism during pregnancy: a systematic review and a meta-analysis of the literature: a reply to a rebuttal. J Thromb Haemost. 2013 Apr;11(4):788–789.
  • Greer IA, Nelson-Piercy C. Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy. Blood. 2005 Jul 15;106(2):401–407.
  • Patel JP, Green B, Patel RK, et al. Population pharmacokinetics of enoxaparin during the antenatal period. Circulation. 2013 Sep 24;128(13):1462–1469.
  • Turrentine MA, Braems G, Ramirez MM. Use of thrombolytics for the treatment of thromboembolic disease during pregnancy. Obstet Gynecol Surv. 1995 Jul;50(7):534–541.
  • Leonhardt G, Gaul C, Nietsch HH, et al. Thrombolytic therapy in pregnancy. J Thromb Thrombolysis. 2006 Jun;21(3):271–276.
  • Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. Lancet. 2015 May 23;385(9982):2077–2087.
  • Chai-Adisaksopha C, Hillis C, Siegal DM, et al. Prothrombin complex concentrates versus fresh frozen plasma for warfarin reversal. A systematic review and meta-analysis. Thromb Haemost. 2016 Oct 28;116(5):879–890.
  • Marlu R, Hodaj E, Paris A, et al. Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb Haemost. 2012 Aug;108(2):217–224.
  • Eerenberg ES, Kamphuisen PW, Sijpkens MK, et al. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011 Oct 4;124(14):1573–1579.
  • Dibu JR, Weimer JM, Ahrens C, et al. The role of FEIBA in reversing novel oral anticoagulants in intracerebral hemorrhage. Neurocrit Care. 2016 Jun;24(3):413–419.
  • Honickel M, Maron B, Van Ryn J, et al. Therapy with activated prothrombin complex concentrate is effective in reducing dabigatran-associated blood loss in a porcine polytrauma model. Thromb Haemost. 2016 Jan;115(2):271–284.
  • Ruff CT, Giugliano RP, Antman EM. Management of bleeding with non-vitamin k antagonist oral anticoagulants in the era of specific reversal agents. Circulation. 2016 Jul 19;134(3):248–261.
  • Pollack CV Jr., Reilly PA, Eikelboom J, et al. Idarucizumab for Dabigatran Reversal. N Engl J Med. 2015 Aug 6;373(6):511–520.
  • Siegal DM, Curnutte JT, Connolly SJ, et al. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N Engl J Med. 2015 Dec 17;373(25):2413–2424.
  • Connolly SJ, Milling TJ Jr, Eikelboom JW, et al. Andexanet alfa for acute major bleeding associated with factor xa inhibitors. N Engl J Med. 2016 Sep 22;375(12):1131–1141.
  • Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 Sep 8;365(10):883–891.
  • Martinelli I, Lensing AW, Middeldorp S, et al. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use. Blood. 2016 Mar 17;127(11):1417–1425.
  • Cohen H, Dore CJ, Clawson S, et al. Rivaroxaban in antiphospholipid syndrome (RAPS) protocol: a prospective, randomized controlled phase II/III clinical trial of rivaroxaban versus warfarin in patients with thrombotic antiphospholipid syndrome, with or without SLE. Lupus. 2015 Sep;24(10):1087–1094.
  • Linkins LA, Warkentin TE, Pai M, et al. Design of the rivaroxaban for heparin-induced thrombocytopenia study. J Thromb Thrombolysis. 2014 Nov;38(4):485–492.
  • Ruff CT, Giugliano RP, Braunwald E, et al. Association between edoxaban dose, concentration, anti-Factor Xa activity, and outcomes: an analysis of data from the randomised, double-blind ENGAGE AF-TIMI 48 trial. Lancet. 2015 Jun 6;385(9984):2288–2295.
  • Di Nisio M, Vedovati MC, Riera-Mestre A, et al. Treatment of venous thromboembolism with rivaroxaban in relation to body weight. A sub-analysis of the EINSTEIN DVT/PE studies. Thromb Haemost. 2016 Sep 27;116(4):739–746.
  • Buller HR, Bethune C, Bhanot S, et al. Factor XI antisense oligonucleotide for prevention of venous thrombosis. N Engl J Med. 2015 Jan 15;372(3):232–240.

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