DVT prophylaxis - antithrombotics - elective major knee surgery clinical trials results meta-analysis

<h1> <a href="TM18-8-antithrombotics-DVTprophylaxis.html"> <strong>DVT prophylaxis</strong> - antithrombotics </a> - elective major knee surgery trial results systematic overview and meta-analysis </h1> <h2>Main characteristics of the included studies</h2> <table> <tr> <th>Trial</th> <th>Treatments</th> <th>Patients</th> <th>Methods</th> </tr> <tr> <td> <a href="index.html"> Leclerc, 1991 </a> <br> </td> <td> Enoxaparin 3000 x2<br>  <i>versus</i> <br> Placebo </td> <td> Knee </td> <td> follow-up 14 days<br> n=65/64<br> <br> double blind <br> </td> </tr> <tr> <td> <a href="index.html"> Levine, 1996 </a> <br> </td> <td> ardeparin 50/kgx2 +elastic stockings<br>  <i>versus</i> <br> Placebo+elastic stockings </td> <td> Knee </td> <td> follow-up 14 days<br> n=122/124<br> <br> double blind <br> </td> </tr> <tr> <td> <a href="index.html"> RE-MOBILIZE (220mg), 2008 </a> <br> </td> <td> dabigatran etexilate 220 mg for 12-15 days <br>  <i>versus</i> <br> Enoxaparin 30 BID </td> <td> Total knee replacement </td> <td> follow-up 12-15 days, median 14d<br> n=862/876<br> <br> double blind <br> US, Canada, Mexico, UK </td> </tr> <tr> <td> <a href="index.html"> RE-MODEL (220mg), 2007 </a> <br> </td> <td> dabigatran etexilate 220 mg q.d. 6-10 days <br>  <i>versus</i> <br> Enoxaparin 40 mg q.d. </td> <td> Total knee replacement </td> <td> follow-up 6-10 days, mean 8 days<br> n=694/699<br> <br> double blind <br> Europe, Australia, South Africa </td> </tr> <tr> <td> <a href="index.html"> RE-MODEL (150mg), 2007 </a> <br> </td> <td> dabigatran etexilate 150 mg q.d. for 6-10 days<br>  <i>versus</i> <br> Enoxaparin 40 mg q.d. </td> <td> Total knee replacement </td> <td> follow-up 6-10 days, mean 8 days<br> n=708/699<br> Parallel groups<br> double blind <br> Europe, Australia, South Africa </td> </tr> <tr> <td> <a href="index.html"> RE-MOBILIZE (150mg), 2008 </a> <br> </td> <td> dabigatran etexilate 150 mg q.d. for 12-15 days<br>  <i>versus</i> <br> Enoxaparin 40 mg q.d. for 12-15 days </td> <td> Total knee replacement </td> <td> follow-up 12-15 days, median 14d<br> n=877/876<br> Parallel groups<br> double blind <br> US, Canada, Mexico, UK </td> </tr> <tr> <td> <a href="index.html"> PENTAMAKS (Bauer), 2001 </a> <br> </td> <td> fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery<br>  <i>versus</i> <br> enoxaparin 30mg twice daily (North america recommendation) </td> <td> elective major knee surgery </td> <td> follow-up 11 days<br> n=517/517<br> Parallel groups<br> double blind <br> North america </td> </tr> <tr> <td> <a href="index.html"> Phase II (Heit), 2001 </a> <br> </td> <td> Ximelagatran 8, 12, 18 or 24 mgorally b.d., at least 12 h after surgery for 6�12 days<br>  <i>versus</i> <br> Enoxaparin 30 mg s.c. b.d.,starting at least 12 h after surgery for 6�12 days </td> <td> adults (age>18 years and weight at least 40 kg) undergoing knee replacements </td> <td> follow-up 6�12 days<br> n=600/0<br> parallel group<br> double-blind <br> North American </td> </tr> <tr> <td> <a href="index.html"> METHRO I, 2002 </a> <br> </td> <td> Melagatran 1�4 mg s.c. immediately before surgery, melagatran at 20.00 hours, then ximelagatran 6�24 mg orally b.d. for 6�9 days<br>  <i>versus</i> <br> Dalteparin 5000 IU o.d., started evening before surgery for 6�9 days </td> <td> adults undergoing hip or knee replacement </td> <td> follow-up 6�9 days<br> n=103/0<br> parallel group<br> open <br> Swedish </td> </tr> <tr> <td> <a href="index.html"> METHRO III, 2002 </a> <br> </td> <td> Melagatran 3 mg s.c. 4�12h after surgery, then ximelagatran24 mg orally b.d. for 7�10 days<br>  <i>versus</i> <br> Enoxaparin 40 mg s.c. o.d. 12 h before surgery for 7�10 days </td> <td> hip or knee replacement </td> <td> follow-up 8�11 days<br> n=2788/0<br> <br> double-blind <br> Europe, South Africa </td> </tr> <tr> <td> <a href="index.html"> EXPRESS, 2003 </a> <br> </td> <td> Melagatran 2 mg s.c. up to 30 min before surgery, then melagatran 3 mg at least 8 hafter surgery, then ximelagatran 24 mg orally b.d. for 8�11 days<br>  <i>versus</i> <br> Enoxaparin 40 mg s.c. o.d.,starting 12 h before surgery for 8�11 days </td> <td> hip or knee replacement </td> <td> follow-up 8�11 days<br> n=2835/0<br> parallel group<br> double-blind <br> Europe </td> </tr> <tr> <td> <a href="index.html"> McKenna-I, 1980 </a> <br> </td> <td> A975,A3900<br>  <i>versus</i> <br> placebo </td> <td> total knee replacement </td> <td> follow-up 2 weeks<br> n=24/12<br> <br> <br> </td> </tr> <tr> <td> <a href="index.html"> ODIXa-KNEE, 2005 </a> <br> </td> <td> BAY 59-7939 5mg b.i.d. for 5�9 days<br>  <i>versus</i> <br> enoxaparin 30 mg b.i.d. for 5�9 days </td> <td> patients undergoing elective total knee replacement </td> <td> follow-up 5-9 days<br> n=102/105<br> Parallel groups<br> double blind <br> North America </td> </tr> <tr> <td> <a href="index.html"> RECORD 3, 2008 </a> <br> NCT00361894 </td> <td> rivaroxaban 10 mg once daily for 10- 14 days<br>  <i>versus</i> <br> enoxaparin 40 mg subcutaneous once daily </td> <td> patients undergoing total knee arthroplasty </td> <td> follow-up 13-17 days<br> n=1254/1277<br> Parallel groups<br> double blind <br> 19 countries worldwide </td> </tr> <tr> <td> <a href="index.html"> RECORD 4, 2009 </a> <br> NCT00362232 </td> <td> rivaroxaban 10mg once daily for 10 to 14 days<br>  <i>versus</i> <br> enoxaparin 30 mg twice daily by subcutaneous injection for 10 to 14 days </td> <td> patients who had undergone total-knee-replacement surgery </td> <td> follow-up 40 days<br> n=1584/1564<br> Parallel groups<br> double blind <br> 12 countries </td> </tr> <tr> <td> <a href="index.html"> ADVANCE 2 (CV185-047), 2010 </a> <br> NCT00452530 </td> <td> apixaban 2.5mg twice daily during 12 days<br>  <i>versus</i> <br> enoxaparin 40mg once daily 12 days </td> <td> patients undergoing elective unilateral or bilateral total knee replacement </td> <td> follow-up 12 days<br> n=1528/1529<br> Parallel groups<br> double blind <br> 27 countries </td> </tr> <tr> <td> <a href="index.html"> L8635, 0 </a> <br> </td> <td> Fondaparinux 2.5mg once daily subcutaneously for 7 days<br>  <i>versus</i> <br> enoxaparin 40mg once daily SC for 7 days </td> <td> Taiwanese patients undergoing elective knee replacement </td> <td> follow-up 10 days<br> n=28/23<br> Parallel groups<br> open, blind assessment <br> Taiwan </td> </tr> <tr> <td> <a href="index.html"> CV185-010, 2007 </a> <br> NCT00097357 </td> <td> apixaban 2.5mg BID, 5mg BID, 10mg BID, 5mgQD, 20mg QD for 12 days<br>  <i>versus</i> <br> enoxaparin 30mg twice daily for 12 days </td> <td> patients undergoing elective total knee replacement surgery </td> <td> follow-up 12 days<br> n=-9/-9<br> Parallel groups<br> double blind <br> </td> </tr> </table> <h2>References</h2> <p> <b>Leclerc, 1991 : </b> Leclerc JR, Geerts WH, Desjardins L, Jobin F, Laroche F, Delorme F, Haviernick S, Atkinson S, Bourgouin JPrevention of deep vein thrombosis after major knee surgery--a randomized, double-blind trial comparing a low molecular weight heparin fragment (enoxaparin) to placebo. <i>Thromb Haemost 1992 Apr 2;67:417-23</i> [PMID 1321509] </p> <p> <b>Levine, 1996 : </b> Levine MN, Gent M, Hirsh J, Weitz J, Turpie AG, Powers P, Neemeh J, Willan A, Skingley PArdeparin (low-molecular-weight heparin) vs graduated compression stockings for the prevention of venous thromboembolism. A randomized trial in patients undergoing knee surgery. <i>Arch Intern Med 1996 Apr 22;156:851-6</i> [PMID 8774203] </p> <p> <b>RE-MOBILIZE (220mg), 2008 : </b> The Oral Thrombin Inhibitor Dabigatran Etexilate vs the North American Enoxaparin Regimen for the Prevention of Venous Thromboembolism after Knee Arthroplasty Surgery. <i>J Arthroplasty 2008;:</i> [PMID 18534438] </p> <p> <b>RE-MODEL (220mg), 2007 : </b> Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, K�lebo P, Christiansen AV, Hantel S, Hettiarachchi R, Schnee J, B�ller HROral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. <i>J Thromb Haemost 2007 Nov;5:2178-85</i> [PMID 17764540] </p> <p> <b>RE-MODEL (150mg), 2007 : </b> Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, K�lebo P, Christiansen AV, Hantel S, Hettiarachchi R, Schnee J, B�ller HROral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. <i>J Thromb Haemost 2007;5:2178-85</i> [PMID 17764540] 10.1111/j.1538-7836.2007.02748.x </p> <p> <b>RE-MOBILIZE (150mg), 2008 : </b> Ginsberg JS, Davidson BL, Comp PC, Francis CW, Friedman RJ, Huo MH, Lieberman JR, Muntz JE, Raskob GE, Clements ML, Hantel S, Schnee JM, Caprini JAOral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. <i>J Arthroplasty 2009;24:1-9</i> [PMID 18534438] 10.1016/j.arth.2008.01.132 </p> <p> <b>PENTAMAKS (Bauer), 2001 : </b> Bauer KA, Eriksson BI, Lassen MR, Turpie AGFondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. <i>N Engl J Med 2001 Nov 1;345:1305-10</i> [PMID 11794149] </p> <p> <b>Phase II (Heit), 2001 : </b> Heit JA, Colwell CW, Francis CW, Ginsberg JS, Berkowitz SD, Whipple J, Peters GComparison of the oral direct thrombin inhibitor ximelagatran with enoxaparin as prophylaxis against venous thromboembolism after total knee replacement: a phase 2 dose-finding study. <i>Arch Intern Med 2001;161:2215-21</i> [PMID 11575978] </p> <p> <b>METHRO I, 2002 : </b> Eriksson BI, Arfwidsson AC, Frison L, Eriksson UG, Bylock A, K�lebo P, Fager G, Gustafsson DA dose-ranging study of the oral direct thrombin inhibitor, ximelagatran, and its subcutaneous form, melagatran, compared with dalteparin in the prophylaxis of thromboembolism after hip or knee replacement: METHRO I. MElagatran for THRombin inhibition in Orthopaedic surgery. <i>Thromb Haemost 2002;87:231-7</i> [PMID 11858482] </p> <p> <b>METHRO III, 2002 : </b> Eriksson BI, Agnelli G, Cohen AT, Dahl OE, Mouret P, Rosencher N, Eskilson C, Nylander I, Frison L, Ogren MDirect thrombin inhibitor melagatran followed by oral ximelagatran in comparison with enoxaparin for prevention of venous thromboembolism after total hip or knee replacement. <i>Thromb Haemost 2003;89:288-96</i> [PMID 12574809] </p> <p> <b>METHRO III, 2002 : </b> Mouret P[The oral direct thrombin inhibitor Ximelagatran Prophylaxis of venous thromboembolism in hip and knee replacement] <i>Hamostaseologie 2002;22:21-4</i> [PMID 12215757] </p> <p> <b>METHRO III, 2002 : </b> Eriksson BIClinical experience of melagatran/ximelagatran in major orthopaedic surgery. <i>Thromb Res 2003;109 Suppl 1:S23-9</i> [PMID 12818631] </p> <p> <b>EXPRESS, 2003 : </b> Eriksson BI, Agnelli G, Cohen AT, Dahl OE, Lassen MR, Mouret P, Rosencher N, K�lebo P, Panfilov S, Eskilson C, Andersson M, Freij AThe direct thrombin inhibitor melagatran followed by oral ximelagatran compared with enoxaparin for the prevention of venous thromboembolism after total hip or knee replacement: the EXPRESS study. <i>J Thromb Haemost 2003;1:2490-6</i> [PMID 14675083] </p> <p> <b>EXPRESS, 2003 : </b> Glynn OThe express study: preliminary results. <i>Int J Clin Pract 2003;57:57-9</i> [PMID 12587945] </p> <p> <b>McKenna-I, 1980 : </b> McKenna R, Galante J, Bachmann F, Wallace DL, Kaushal PS, Meredith PPrevention of venous thromboembolism after total knee replacement by high-dose aspirin or intermittent calf and thigh compression. <i>Br Med J 1980;280:514-7</i> [PMID 6989432] </p> <p> <b>ODIXa-KNEE, 2005 : </b> Turpie AG, Fisher WD, Bauer KA, Kwong LM, Irwin MW, K�lebo P, Misselwitz F, Gent MBAY 59-7939: an oral, direct factor Xa inhibitor for the prevention of venous thromboembolism in patients after total knee replacement. A phase II dose-ranging study. <i>J Thromb Haemost 2005 Nov;3:2479-86</i> [PMID 16241946] </p> <p> <b>CV185-010, 2007 : </b> Lassen MR, Davidson BL, Gallus A, Pineo G, Ansell J, Deitchman DThe efficacy and safety of apixaban, an oral, direct factor Xa inhibitor, as thromboprophylaxis in patients following total knee replacement. <i>J Thromb Haemost 2007 Dec;5:2368-75</i> [PMID 17868430] </p> <p> <b>RECORD 3, 2008 : </b> Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F, Turpie AGRivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. <i>N Engl J Med 2008 Jun 26;358:2776-86</i> [PMID 18579812] </p> <p> <b>RECORD 4, 2009 : </b> Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, Cushner FD, Lotke PA, Berkowitz SD, Bandel TJ, Benson A, Misselwitz F, Fisher WDRivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. <i>Lancet 2009;:</i> [PMID 19411100] </p> <p> <b>CV185-034, : </b> Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Portman RJApixaban or enoxaparin for thromboprophylaxis after knee replacement. <i>N Engl J Med 2009;361:594-604</i> [PMID 19657123] </p> <p> <b>ADVANCE 2 (CV185-047), 2010 : </b> Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick PApixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. <i>Lancet 2010 Mar 6;375:807-15</i> [PMID 20206776] 10.1016/S0140-6736(09)62125-5 </p>