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DOI: 10.1160/TH16-08-0595
Efficacy and safety of extended thromboprophylaxis for medically ill patients
A meta-analysis of randomised controlled trialsPublication History
Received:
03 August 2016
Accepted after major revision:
10 January 2016
Publication Date:
21 November 2017 (online)
Summary
Compelling evidence suggests that the risk of pulmonary embolism (PE) and deep-vein thrombosis (DVT) persists after hospital discharge in acutely-ill medical patients. However, no studies consistently supported the routine use of extended-duration thromboprophylaxis (ET) in this setting. We performed a meta-analysis to assess efficacy and safety of ET in acutely-ill medical patients. Efficacy outcome was defined by the prevention of symptomatic DVT, PE, venous thromboembolism (VTE) and VTE-related mortality. Safety outcome was the occurrence of major bleeding (MB) and fatal bleeding (FB). Pooled odds ratios (ORs) and 95 % confidence intervals (95 %CI) were calculated for each outcome using a random effects model. Four RCTs for a total of 28,105 acutely-ill medical patients were included. ET was associated with a significantly lower risk of DVT (0.3 % vs 0.6 %, OR 0.504, 95 %CI: 0.287–0.885) and VTE (0.5 % vs 1.0 %, OR: 0.544, 95 %CI: 0.297–0.997); a non-significantly lower risk of PE (0.3 % vs 0.4 %, OR 0.633, 95 %CI: 0.388–1.034) and of VTE-related mortality (0.2 % vs 0.3 %, OR 0.687, 95 %CI: 0.445–1.059) and with a significantly higher risk of MB (0.8 % vs 0.4 %, OR 2.095, 95 %CI: 1.333–3.295). No difference in FB was found (0.06 % vs 0.03 %, OR 1.79, 95 %CI: 0.384–8.325). The risk benefit analysis showed that the NNT for DVT was 339, for VTE was 239, and the NNH for MB was 247. Results of our meta-analyses focused on clinical important outcomes did not support a general use of antithrombotic prophylaxis beyond the period of hospitalization in acutely-ill medical patients.
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References
- 1 Cohen AT, Alikhan R, Arcelus JI. et al. Assessment of venous thromboembolism risk and the benefits of thromboprophylaxis in medical patients. Thromb Haemost 2005; 94: 750-759.
- 2 Geerts WH, Bergqvist D, Pineo GF. et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133: 381S-453S.
- 3 Samama MM, Cohen AT, Darmon JY. et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group. N Engl J Med 1999; 341: 793-800.
- 4 Alikhan R, Cohen AT, Combe S. et al. Risk factors for venous thromboembolism in hospitalized patients with acute medical illness: analysis of the MEDENOX Study. Arch Intern Med 2004; 164: 963-968.
- 5 Cohen AT, Spiro TE, Spyropoulos AC. et al. D-dimer as a predictor of venous thromboembolism in acutely ill, hospitalized patients: a subanalysis of the randomized controlled MAGELLAN trial. J Thromb Haemost 2014; 12: 479-487.
- 6 Hull RD, Schellong SM, Tapson VF. et al. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med 2010; 153: 8-18.
- 7 Leizorovicz A, Cohen AT, Turpie AG. et al. Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 2004; 110: 874-879.
- 8 Cohen AT, Davidson BL, Gallus AS. et al. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. Br Med J 2006; 332: 325-329.
- 9 Violi F, Perri L, Loffredo L. Should all acutely ill medical patients be treated with antithrombotic drugs? A review of the interventional trials. Thromb Haemost 2013; 109: 589-595.
- 10 Baglin TP, White K, Charles A. Fatal pulmonary embolism in hospitalised medical patients. J Clin Pathol 1997; 50: 609-610.
- 11 Dentali F, Douketis JD, Gianni M. et al. Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients. Ann Intern Med 2007; 146: 278-288.
- 12 Fraisse F, Holzapfel L, Couland JM. et al. Nadroparin in the prevention of deep vein thrombosis in acute decompensated COPD. The Association of Non-University Affiliated Intensive Care Specialist Physicians of France. Am J Respir Crit Care Med 2000; 161: 1109-1114.
- 13 Kahn SR, Lim W, Dunn AS. et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e195S-226S.
- 14 Spencer FA, Lessard D, Emery C. et al. Venous thromboembolism in the outpatient setting. Arch Intern Med 2007; 167: 1471-1475.
- 15 Amin AN, Varker H, Princic N. et al. Duration of venous thromboembolism risk across a continuum in medically ill hospitalized patients. J Hosp Med 2012; 07: 231-238.
- 16 Goldhaber SZ, Leizorovicz A, Kakkar AK. et al. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med 2011; 365: 2167-2177.
- 17 Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the S, Standardisation Committee of the International Society on T, Haemostasis. Definition of major bleeding in clinical investigations of antihaemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 03: 692-694.
- 18 Moher D, Liberati A, Tetzlaff J. et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 2009; 151: 264-269 W64.
- 19 Sterne JA, Egger M, Smith GD. Systematic reviews in health care: Investigating and dealing with publication and other biases in meta-analysis. Br Med J 2001; 323: 101-105.
- 20 Cohen AT, Spiro TE, Buller HR. et al. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med 2013; 368: 513-523.
- 21 Cohen AT, Harrington RA, Goldhaber SZ. et al. Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients. N Engl J Med 2016; 375: 534-544.
- 22 Anderson Jr. FA, 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; 151: 933-938.
- 23 Heit JA, O’Fallon WM, Petterson TM. et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. Arch Intern Med 2002; 162: 1245-1248.
- 24 Bergqvist D, Agnelli G, Cohen AT. et al. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med 2002; 346: 975-980.
- 25 Bergqvist D, Benoni G, Bjorgell O. et al. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996; 335: 696-700.
- 26 Lassen MR, Ageno W, Borris LC. et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008; 358: 2776-2786.
- 27 Sharma A, Chatterjee S, Lichstein E, Mukherjee D. Extended thromboprophylaxis for medically ill patients with decreased mobility: does it improve outcomes?. J Thromb Haemost 2012; 10: 2053-2060.
- 28 Adam SS, Key NS, Greenberg CS. D-dimer antigen: current concepts and future prospects. Blood 2009; 113: 2878-2887.
- 29 Desjardins L, Bara L, Boutitie F. et al. Correlation of plasma coagulation parameters with thromboprophylaxis, patient characteristics, and outcome in the MEDENOX study. Arch Pathol Lab Med 2004; 128: 519-526.
- 30 Fan J, Li X, Cheng Y. et al. Measurement of D-dimer as aid in risk evaluation of VTE in elderly patients hospitalized for acute illness: a prospective, multicenter study in China. Clin Invest Med 2011; 34: E96-104.
- 31 Imberti D, Benedetti R, Ageno W. Prevention of venous thromboembolism in acutely ill medical patients after the results of recent trials with the new oral anticoagulants. Intern Emerg Med 2013; 08: 667-672.
- 32 Spyropoulos AC, Anderson Jr, FA, Fitzgerald G. et al; IMPROVE Investigators. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest 2011; 140: 706-714.
- 33 Rosenberg D, Eichorn A, Alarcon M. et al. External validation of the risk assessment model of the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) for medical patients in a tertiary health system. J Am Heart Assoc 2014; 3: e001152.
- 34 Mahan CE, Liu Y, Turpie AG. et al. External validation of a risk assessment model for venous thromboembolism in the hospitalised acutely-ill medical patient (VTE-VALOURR). Thromb Haemost 2014; 112: 692-699.
- 35 Raskob GE, Spyropoulos AC, Zrubek J. et al. The MARINER trial of rivaroxaban after hospital discharge for medical patients at high risk of VTE Design, rationale, and clinical implications. Thromb Haemost 2016; 115: 1240-1248.