acute coronary syndrome - anticoagulant - All ACS (including AMI) clinical trials results meta-analysis

<h1> <a href="TM16-6-anticoagulant-acute coronary syndrome" > <strong>acute coronary syndrome</strong> - anticoagulant </a> - All ACS (including AMI) 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="../TRC_t8551.htm"> ATACS (pilot study) (warfarin vs control), 1990 </a> <br> </td> <td> heparin/warfarin target INR 3-4.5 + aspirin<br>  <i>versus</i> <br> aspirin alone </td> <td> UA, NSTEMI </td> <td> follow-up 3 months<br> n=37/32<br> <br> open <br> </td> </tr> <tr> <td> <a href="../TRC_t8552.htm"> ATACS , 1994 </a> <br> </td> <td> heparin/warfarin (INR median 2.3) + aspirin<br>  <i>versus</i> <br> aspirin </td> <td> UA, NSTEMI </td> <td> follow-up 3 months<br> n=105/109<br> <br> open <br> </td> </tr> <tr> <td> <a href="../TRC_t8553.htm"> Williams , 1997 </a> <br> </td> <td> warfarin target INR 2–2.5 +aspirin<br>  <i>versus</i> <br> placebo +aspirin </td> <td> UA, AMI </td> <td> follow-up 2.5 months<br> n=29/28<br> <br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t8554.htm"> CARS , 1997 </a> <br> </td> <td> warfarin (INR mean 1.5) (3 mg warfarin or 1 mg warfarin with 80 mg aspirin)<br>  <i>versus</i> <br> aspirin 160 mg/d </td> <td> AMI </td> <td> follow-up 14 months<br> n=5410/3393<br> <br> <br> </td> </tr> <tr> <td> <a href="../TRC_t8555.htm"> OASIS Pilot (phase 1) , 1998 </a> <br> </td> <td> warfarin 3mg/d for 6 months (INR mean 1.5)<br>  <i>versus</i> <br> control </td> <td> UA, NSTEMI </td> <td> follow-up 6 months<br> n=155/154<br> <br> open <br> </td> </tr> <tr> <td> <a href="../TRC_t8556.htm"> OASIS Pilot (phase 2) , 1998 </a> <br> </td> <td> warfarin adjusted dose (INR mean 2.3) for 3 months<br>  <i>versus</i> <br> standard treatment </td> <td> UA, NSTEMI </td> <td> follow-up 3 months<br> n=98/99<br> <br> open <br> </td> </tr> <tr> <td> <a href="../TRC_t8557.htm"> Huyhn , 2001 </a> <br> </td> <td> warfarin adjusted dose for INR 2–2.5 +aspirin<br>  <i>versus</i> <br> placebo +aspirin </td> <td> UA, NSTEMI with prior CABG </td> <td> follow-up 1 year<br> n=44/46<br> <br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t8558.htm"> OASIS-2 Warfarin Substudy, 2001 </a> <br> </td> <td> warfarin target INR 2–2.5 for 5 months +aspirin<br>  <i>versus</i> <br> control </td> <td> UA </td> <td> follow-up 5 months<br> n=1848/1864<br> <br> open <br> </td> </tr> <tr> <td> <a href="../TRC_t8559.htm"> ASPECT-2 (coumadin+asp vs asp), 2002 </a> <br> </td> <td> coumadin(INR mean 2.4) +aspirin<br>  <i>versus</i> <br> aspirin </td> <td> UA, AMI </td> <td> follow-up 1 year<br> n=333/336<br> <br> open <br> the Netherlands </td> </tr> <tr> <td> <a href="../TRC_t8560.htm"> APRICOT-2 , 2002 </a> <br> </td> <td> moderate-intensity coumarin target INR 2-3 (+aspirin)<br>  <i>versus</i> <br> aspirin </td> <td> STEMI </td> <td> follow-up 3 months<br> n=135/139<br> <br> <br> </td> </tr> <tr> <td> <a href="../TRC_t8561.htm"> CHAMP , 2002 </a> <br> </td> <td> warfarin (INR median 1.8)<br>  <i>versus</i> <br> </td> <td> AMI </td> <td> follow-up 2.7 years<br> n=2522/2537<br> <br> <br> </td> </tr> <tr> <td> <a href="../TRC_t8562.htm"> WARIS , 2002 </a> <br> </td> <td> warfarin (INR 2.2 (mean)<br>  <i>versus</i> <br> </td> <td> AMI </td> <td> follow-up 4 years<br> n=1208/1206<br> <br> <br> </td> </tr> <tr> <td> <a href="../TRC_t8563.htm"> LoWASA , 2004 </a> <br> </td> <td> warfarin (prothrombin complex activity mean 95.5)<br>  <i>versus</i> <br> </td> <td> AMI </td> <td> follow-up 5 years<br> n=1659/1641<br> <br> <br> </td> </tr> <tr> <td> <a href="../TRC_t8564.htm"> Zibaeenezhad , 2004 </a> <br> </td> <td> Warfarin target INR 2–3<br>  <i>versus</i> <br> </td> <td> AMI </td> <td> follow-up 1 year<br> n=70/70<br> <br> <br> </td> </tr> <tr> <td> <a href="../TRC_t8580.htm"> ASPECT-2 (coumadin vs aspirin), 2002 </a> <br> </td> <td> coumadin (phenprocoumon or acenocoumarol) target INR 3-4) <br>  <i>versus</i> <br> aspirin 80mg daily </td> <td> UA, AMI </td> <td> follow-up 1 year (range 0-26 months)<br> n=325/336<br> Parallel groups<br> open <br> the Netherlands </td> </tr> <tr> <td> <a href="../TRC_t8581.htm"> ATACS (pilot study) warfarin vs aspirin , 1990 </a> <br> </td> <td> heparin/warfarin target INR 3-4<br>  <i>versus</i> <br> aspirin 325 mg daily </td> <td> UA, NSTEMI </td> <td> follow-up 3 months<br> n=24/32<br> <br> open <br> </td> </tr> <tr> <td> <a href="../TRC_t8586.htm"> APPRAISE-1 (10mg od), 2009 </a> <br> NCT00313300 </td> <td> apixaban 10 mg once daily<br>  <i>versus</i> <br> placebo </td> <td> patients with a recent ST-elevation or non–ST-elevation acute coronary syndrome(<7 days) </td> <td> follow-up 6 months<br> n=318/611<br> Parallel groups<br> double blind <br> Europe, Middle East, North America </td> </tr> <tr> <td> <a href="../TRC_t8614.htm"> APPRAISE-1 (2.5 mg bid), 2009 </a> <br> NCT00313300 </td> <td> Apixaban 2.5mg twice daily <br>  <i>versus</i> <br> placebo </td> <td> patients with a recent ST-elevation or non–ST-elevation acute coronary syndrome(<7 days) </td> <td> follow-up 6 months<br> n=-9/611<br> <br> double blind <br> Europe, Middle East, North America </td> </tr> <tr> <td> <a href="../TRC_t9768.htm"> ATLAS ACS-TIMI 46, 2009 </a> <br> NCT00402597 </td> <td> rivaroxaban 5 mg, 10 mg, or 20 mg once daily, 2.5 mg, 5 mg, or 10 mg twice daily<br>  <i>versus</i> <br> placebo </td> <td> recent ACS patients treated with aspirin alone (n=761) or aspirin plus clopidogrel (n=2730) </td> <td> follow-up 6 months<br> n=2331/1160<br> Parallel groups<br> double blind <br> 27 countries </td> </tr> <tr> <td> <a href="../TRC_t9882.htm"> SEPIA-ACS1 TIMI 42, 2009 </a> <br> NCT00317395 </td> <td> otamixaban 5 doses (0·08 mg/kg bolus followed by 0.035, 0.070, 0.105, 0.140, 0.175 mg/kg/h)<br>  <i>versus</i> <br> Heparin+eptifibatide </td> <td> patients with non-ST-elevation acute coronary syndromes </td> <td> follow-up 7 days<br> n=2792/449<br> Parallel groups<br> double blind <br> 36 countries </td> </tr> <tr> <td> <a href="../TRC_t10003.htm"> ATLAS ACS TIMI 51, </a> <br> NCT00809965 </td> <td> rivaroxaban (2.5 mg twice daily or 5 mg twice daily) in addition to standard care<br>  <i>versus</i> <br> placebo </td> <td> patients with a recent ACS </td> <td> follow-up <br> n=16000/0<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t10337.htm"> B0661004, </a> <br> NCT00852397 </td> <td> Apixaban 2.5 or 5 mg twice daily<br>  <i>versus</i> <br> placebo </td> <td> patients with recent (<=7 Days) acute coronary syndrome </td> <td> follow-up 24 weeks<br> n=-9/-9<br> Parallel groups<br> double blind <br> japan </td> </tr> <tr> <td> <a href="../TRC_t10338.htm"> APPRAISE 2 (CV185-068), </a> <br> NCT00831441 </td> <td> apixaban 5mg twice daily<br>  <i>versus</i> <br> placebo </td> <td> patients with a recent acute coronary syndrome </td> <td> follow-up <br> n=10848/0<br> Parallel groups<br> double blind <br> </td> </tr> </table> <h2>References</h2> <p> <b>ATACS (pilot study) (warfarin vs control), 1990 : </b> Cohen M, Adams PC, Hawkins L, Bach M, Fuster VUsefulness of antithrombotic therapy in resting angina pectoris or non-Q-wave myocardial infarction in preventing death and myocardial infarction (a pilot study from the Antithrombotic Therapy in Acute Coronary Syndromes Study Group). <i>Am J Cardiol 1990;66:1287-92</i> [PMID 2244556] </p> <p> <b>ATACS , 1994 : </b> Cohen M, Adams PC, Parry G, Xiong J, Chamberlain D, Wieczorek I, Fox KA, Chesebro JH, Strain J, Keller CCombination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users. Primary end points analysis from the ATACS trial. Antithrombotic Therapy in Acute Coronary Syndromes Research Group. <i>Circulation 1994;89:81-8</i> [PMID 8281698] </p> <p> <b>Williams , 1997 : </b> Williams MJ, Morison IM, Parker JH, Stewart RAProgression of the culprit lesion in unstable coronary artery disease with warfarin and aspirin versus aspirin alone: preliminary study. <i>J Am Coll Cardiol 1997;30:364-9</i> [PMID 9247506] </p> <p> <b>CARS , 1997 : </b> Randomised double-blind trial of fixed low-dose warfarin with aspirin after myocardial infarction. Coumadin Aspirin Reinfarction Study (CARS) Investigators. <i>Lancet 1997;350:389-96</i> [PMID 9259652] </p> <p> <b>OASIS Pilot (phase 1) , 1998 : </b> Anand SS, Yusuf S, Pogue J, Weitz JI, Flather MLong-term oral anticoagulant therapy in patients with unstable angina or suspected non-Q-wave myocardial infarction: organization to assess strategies for ischemic syndromes (OASIS) pilot study results. <i>Circulation 1998;98:1064-70</i> [PMID 9736592] </p> <p> <b>OASIS Pilot (phase 2) , 1998 : </b> Anand SS, Yusuf S, Pogue J, Weitz JI, Flather MLong-term oral anticoagulant therapy in patients with unstable angina or suspected non-Q-wave myocardial infarction: organization to assess strategies for ischemic syndromes (OASIS) pilot study results. <i>Circulation 1998;98:1064-70</i> [PMID 9736592] </p> <p> <b>Huyhn , 2001 : </b> Huynh T, Théroux P, Bogaty P, Nasmith J, Solymoss SAspirin, warfarin, or the combination for secondary prevention of coronary events in patients with acute coronary syndromes and prior coronary artery bypass surgery. <i>Circulation 2001;103:3069-74</i> [PMID 11425770] </p> <p> <b>OASIS-2 Warfarin Substudy, 2001 : </b> Effects of long-term, moderate-intensity oral anticoagulation in addition to aspirin in unstable angina. The Organization to Assess Strategies for Ischemic Syndromes (OASIS) Investigators. <i>J Am Coll Cardiol 2001;37:475-84</i> [PMID 11216966] </p> <p> <b>ASPECT-2 (coumadin+asp vs asp), 2002 : </b> van Es RF, Jonker JJ, Verheugt FW, Deckers JW, Grobbee DEAspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial. <i>Lancet 2002;360:109-13</i> [PMID 12126819] </p> <p> <b>APRICOT-2 , 2002 : </b> Brouwer MA, van den Bergh PJ, Aengevaeren WR, Veen G, Luijten HE, Hertzberger DP, van Boven AJ, Vromans RP, Uijen GJ, Verheugt FWAspirin plus coumarin versus aspirin alone in the prevention of reocclusion after fibrinolysis for acute myocardial infarction: results of the Antithrombotics in the Prevention of Reocclusion In Coronary Thrombolysis (APRICOT)-2 Trial. <i>Circulation 2002;106:659-65</i> [PMID 12163424] </p> <p> <b>CHAMP , 2002 : </b> Fiore LD, Ezekowitz MD, Brophy MT, Lu D, Sacco J, Peduzzi PDepartment of Veterans Affairs Cooperative Studies Program Clinical Trial comparing combined warfarin and aspirin with aspirin alone in survivors of acute myocardial infarction: primary results of the CHAMP study. <i>Circulation 2002;105:557-63</i> [PMID 11827919] </p> <p> <b>WARIS , 2002 : </b> Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen HWarfarin, aspirin, or both after myocardial infarction. <i>N Engl J Med 2002;347:969-74</i> [PMID 12324552] </p> <p> <b>LoWASA , 2004 : </b> Herlitz J, Holm J, Peterson M, Karlson BW, Haglid Evander M, Erhardt LEffect of fixed low-dose warfarin added to aspirin in the long term after acute myocardial infarction; the LoWASA Study. <i>Eur Heart J 2004;25:232-9</i> [PMID 14972424] </p> <p> <b>Zibaeenezhad , 2004 : </b> Zibaeenezhad MJ, Mowla A, Sorbi MHWarfarin and aspirin versus aspirin alone in patients with acute myocardial infarction: a pilot study. <i>Angiology 2004;55:17-20</i> [PMID 14759085] </p> <p> <b>ATACS (pilot study) warfarin vs aspirin , 1990 : </b> Cohen M, Adams PC, Hawkins L, Bach M, Fuster VUsefulness of antithrombotic therapy in resting angina pectoris or non-Q-wave myocardial infarction in preventing death and myocardial infarction (a pilot study from the Antithrombotic Therapy in Acute Coronary Syndromes Study Group). <i>Am J Cardiol 1990;66:1287-92</i> [PMID 2244556] </p> <p> <b>APPRAISE-1 (10mg od), 2009 : </b> Apixaban, an Oral, Direct, Selective Factor Xa Inhibitor, in Combination With Antiplatelet Therapy After Acute Coronary Syndrome. Results of the Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) Trial. <i>Circulation 2009;:</i> [PMID 19470889] </p> <p> <b>APPRAISE-1 (2.5 mg bid), 2009 : </b> <i>Circulation 2009;:</i> [PMID 19470889] </p> <p> <b>ATLAS ACS-TIMI 46, 2009 : </b> Mega JL, Braunwald E, Mohanavelu S, Burton P, Poulter R, Misselwitz F, Hricak V, Barnathan ES, Bordes P, Witkowski A, Markov V, Oppenheimer L, Gibson CMRivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial. <i>Lancet 2009 Jul 4;374:29-38</i> [PMID 19539361] </p> <p> <b>SEPIA-ACS1 TIMI 42, 2009 : </b> Sabatine MS, Antman EM, Widimsky P, Ebrahim IO, Kiss RG, Saaiman A, Polasek R, Contant CF, McCabe CH, Braunwald EOtamixaban for the treatment of patients with non-ST-elevation acute coronary syndromes (SEPIA-ACS1 TIMI 42): a randomised, double-blind, active-controlled, phase 2 trial. <i>Lancet 2009 Aug 28;:</i> [PMID 19717184] 10.1016/S0140-6736(09)61454-9 </p>