atrial fibrillation - antithrombotics - primary prevention of thromboembolic events clinical trials results meta-analysis

<h1> <a href="index.html"> <strong>atrial fibrillation</strong> - antithrombotics </a> - primary prevention of thromboembolic events 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"> PATAF (vs coumadin low dose), 1999 </a> <br> </td> <td> aspirin 300mg/d<br>  <i>versus</i> <br> coumarin low dose(target INR 1.1-1.6 ) </td> <td> non rheumatic AF,recruited in general practice,with no established indication for anticoagulation. </td> <td> follow-up 2.7 years<br> n=319/279<br> Parallel groups<br> Simple aveugle <br> Netherlands </td> </tr> <tr> <td> <a href="index.html"> AFASAK II (aspirin vs warfarin low dose), 1998 </a> <br> </td> <td> aspirin 300 mg/d<br>  <i>versus</i> <br> warfarin low dose (1.25mg/d) </td> <td> chronic non valvular atrial fibrillation </td> <td> follow-up 3.5 years<br> n=169/167<br> Parallel groups<br> Open <br> Denmark </td> </tr> <tr> <td> <a href="index.html"> PATAF (coumadin low dose vs coumadin standard dose), 1999 </a> <br> </td> <td> coumarin low dose(target INR 1.1-1.6)<br>  <i>versus</i> <br> coumarin standard dose(target INR 2.5-3.5) </td> <td> non rheumatic AF,recruited in general practice,with no established indication for anticoagulation. </td> <td> follow-up 2.7 years<br> n=122/131<br> Parallel groups<br> Simple aveugle <br> Netherlands </td> </tr> <tr> <td> <a href="index.html"> AFASAK II (warfarin low dose vs warfarin standard dose), 1998 </a> <br> </td> <td> warfarin fixed low dose (1.25 mg/d)<br>  <i>versus</i> <br> warfarin standard dose(target INR 2-3) </td> <td> chronic non valvular atrial fibrillation </td> <td> follow-up 3.5 years<br> n=167/170<br> Parallel groups<br> Open <br> Denmark </td> </tr> <tr> <td> <a href="index.html"> AFASAK II (warfarin low dose+aspirin vs warfarin standard dose), 1998 </a> <br> </td> <td> warfarin fixed low dose(1.25mg/d) + aspirin(300mg/d)<br>  <i>versus</i> <br> warfarin standard dose(target INR 2.0-3.0) </td> <td> chronic non valvular atrial fibrillation </td> <td> follow-up 3.5 years<br> n=171/170<br> Parallel groups<br> Open <br> Denmark </td> </tr> <tr> <td> <a href="index.html"> SPAF III, 1996 </a> <br> </td> <td> warfarin low dose(target INR 1.2-1.5)+ aspirin 325 mg/d<br>  <i>versus</i> <br> warfarin standard dose(target INR 2.0-3.0) </td> <td> non rheumatic atrial fibrillation,patients with at least one additional thromboembolic risk factor(high risk patients) </td> <td> follow-up 1.1 years<br> n=521/523<br> Parallel groups<br> Open <br> USA,Canada </td> </tr> <tr> <td> <a href="index.html"> SPAF II (aspirin vs warfarin standard dose, age<75), 1994 </a> <br> </td> <td> aspirin 325 mg/d<br>  <i>versus</i> <br> warfarin standard dose(target INR 2.0-4.5) </td> <td> non rheumatic atrial fibrillation,medium to high risk patients. Patients aged 75 and less. </td> <td> follow-up 3.1 years<br> n=357/358<br> Parallel groups<br> Open <br> USA </td> </tr> <tr> <td> <a href="index.html"> AFASAK II (aspirin vs warfarin standard dose), 1998 </a> <br> </td> <td> aspirin 300 mg/d<br>  <i>versus</i> <br> warfarin standard dose(target INR 2-3) </td> <td> chronic non valvular atrial fibrillation </td> <td> follow-up 3.5 years<br> n=169/170<br> Parallel groups<br> Open <br> Denmark </td> </tr> <tr> <td> <a href="index.html"> PATAF (vs coumadin standard dose), 1999 </a> <br> </td> <td> aspirin 150mg/d<br>  <i>versus</i> <br> coumarin standard dose(target INR 2.5-3.5) </td> <td> non rheumatic AF,recruited in general practice,with no established indication for anticoagulation. </td> <td> follow-up 2.7 years<br> n=141/131<br> Parallel groups<br> Simple aveugle <br> Netherlands </td> </tr> <tr> <td> <a href="index.html"> SPAF II (aspirin vs warfarin standard dose, age>75), 1994 </a> <br> </td> <td> aspirin 325 mg/d<br>  <i>versus</i> <br> warfarin standard dose (target INR 2.0-4.5) </td> <td> Non rheumatic atrial fibrillation,medium to high risk patients.Patients aged more than 75. </td> <td> follow-up 2.0 years<br> n=188/197<br> Parallel groups<br> Open <br> USA </td> </tr> <tr> <td> <a href="index.html"> AFASAK (aspirin vs placebo), 1989 </a> <br> </td> <td> aspirin 75 mg/d <br>  <i>versus</i> <br> placebo </td> <td> patients with chronic non-rheumatic atrial fibrillation </td> <td> follow-up 2 years<br> n=336/336<br> Parallel groups<br> Double aveugle <br> Denmark </td> </tr> <tr> <td> <a href="index.html"> LASAF(aspirin vs no treatment), 1999 </a> <br> </td> <td> aspirin:125mg/day(group A1);125mg on alternate days(group A2) <br>  <i>versus</i> <br> no control treatment(group C) </td> <td> </td> <td> follow-up <br> n=-9/-9<br> <br> Open <br> </td> </tr> <tr> <td> <a href="index.html"> SPAF (aspirin,warfarin ineligible arm), 1991 </a> <br> </td> <td> aspirin 325mg/d <br>  <i>versus</i> <br> placebo </td> <td> nonrheumatic atrial fibrillation, warfarin ineligible patients </td> <td> follow-up 1.3 years<br> n=346/357<br> Parallel groups<br> Double blind <br> USA </td> </tr> <tr> <td> <a href="index.html"> CAFA, 1991 </a> <br> </td> <td> warfarin standard dose (target INR 2-3)<br>  <i>versus</i> <br> placebo </td> <td> non rheumatic atrial fibrillation </td> <td> follow-up 15.2 months<br> n=187/191<br> Parallel groups<br> Double blind <br> canada </td> </tr> <tr> <td> <a href="index.html"> AFASAK (warfarin standard dose vs control), 1989 </a> <br> </td> <td> warfarin standard dose(target INR:2.8-4.2)<br>  <i>versus</i> <br> control </td> <td> chronic non rheumatic AF </td> <td> follow-up 2 years<br> n=335/336<br> Parallel groups<br> Open <br> Denmark </td> </tr> <tr> <td> <a href="index.html"> BAATAF (warfarin vs no treatment), 1990 </a> <br> NCT00000517 </td> <td> warfarin low dose (target INR:1.5-2.7)<br>  <i>versus</i> <br> no placebo.people received no treatment but could choose to take aspirin. </td> <td> non rheumatic AF </td> <td> follow-up 2.2 years<br> n=212/208<br> Parallel groups<br> Open <br> </td> </tr> <tr> <td> <a href="index.html"> SPAF (warfarin standard dose), 1991 </a> <br> </td> <td> warfarin standard dose(target INR:2.0-4.5)<br>  <i>versus</i> <br> control </td> <td> </td> <td> follow-up 1.3 years<br> n=210/211<br> Parallel groups<br> Open <br> USA </td> </tr> <tr> <td> <a href="index.html"> SPINAF (warfarin vs placebo), 1992 </a> <br> </td> <td> warfarin low dose(target INR 1.4-2.8) <br>  <i>versus</i> <br> placebo </td> <td> men ,with chronic nonrheumatic atrial fibrillation </td> <td> follow-up 1.75 years<br> n=260/265<br> Parallel groups<br> Double blind <br> usa </td> </tr> <tr> <td> <a href="index.html"> SPORTIF II (ximelagatran vs warfarin standard dose), 2002 </a> <br> </td> <td> ximelegatran 20,40,60 mg twice daily<br>  <i>versus</i> <br> warfarin standard dose(target INR 2-3) </td> <td> Medium to high risk patients with chronic non valvular atrial fibrillation. </td> <td> follow-up 16 weeks<br> n=187/67<br> Parallel groups<br> Open <br> Europe ,USA </td> </tr> <tr> <td> <a href="index.html"> SPORTIF III, 2003 </a> <br> </td> <td> ximelagatran 36 mg twice daily<br>  <i>versus</i> <br> warfarin standard dose (target INR 2-3) </td> <td> One or more stroke risk factor in addition to AF.High risk patients with non valvular atrial fibrillation. </td> <td> follow-up 17.4 months<br> n=1704/1703<br> Parallel groups<br> Open <br> europe,asia,australasia </td> </tr> <tr> <td> <a href="index.html"> SPORTIF V, 2005 </a> <br> </td> <td> ximelegatran 36 mg twice daily<br>  <i>versus</i> <br> warfarin standard dose(target INR 2-3) </td> <td> One or more stroke risk factor in addition to atrial fibrillation.High risk patients with non valvular atrial fibrillation. </td> <td> follow-up 20 months<br> n=1960/1962<br> Parallel groups<br> Double blind <br> north america </td> </tr> <tr> <td> <a href="index.html"> MWNAF, 1998 </a> <br> </td> <td> warfarin low dose (1.25mg/d)<br>  <i>versus</i> <br> warfarin standard dose( target INR 2.0-3.0) </td> <td> Patients over 60 with non rheumatic atrial fibrillation </td> <td> follow-up 14.5 months<br> n=150/153<br> Parallel groups<br> Open <br> Italy </td> </tr> <tr> <td> <a href="index.html"> NASPEAF (triflusal + coumadin medium dose vs coumadin standard dose), 2004 </a> <br> </td> <td> Triflusal 600 mg/d + coumadin medium dose (target INR 1.25-2) <br>  <i>versus</i> <br> coumadin standard dose(target INR 2-3) </td> <td> Non valvular atrial fibrillation. Intermediate risk patients. </td> <td> follow-up 2.76 years<br> n=235/237<br> Parallel groups<br> Open <br> Spain </td> </tr> <tr> <td> <a href="index.html"> SAFT(warfarin low dose + aspirin vs no treatment), 2003 </a> <br> </td> <td> warfarin low dose (1.25 mg/d) + aspirin 75 mg/d<br>  <i>versus</i> <br> no treatment </td> <td> Low-medium risk patients with non valvular atrial fibrillation. </td> <td> follow-up 33 months<br> n=334/334<br> Parallel groups<br> Open <br> Sweden </td> </tr> <tr> <td> <a href="index.html"> NASPEAF (triflusal vs coumadin standard dose)), 2004 </a> <br> </td> <td> Triflusal 600 mg/d<br>  <i>versus</i> <br> coumadin standard dose(target INR 2-3) </td> <td> Non valvular atrial fibrillation. Intermediate risk patients. </td> <td> follow-up 2.76 years<br> n=242/237<br> Parallel groups<br> Open <br> Spain </td> </tr> <tr> <td> <a href="index.html"> NASPEAF (triflusal+coumadin medium dose vs triflusal), 2004 </a> <br> </td> <td> Triflusal 600 mg/d + coumadin medium dose (target INR 1.25-2) <br>  <i>versus</i> <br> Triflusal 600 mg/d </td> <td> Non valvular atrial fibrillation. Intermediate risk patients </td> <td> follow-up 2.76 years<br> n=235/242<br> Parallel groups<br> Open <br> Spain </td> </tr> <tr> <td> <a href="index.html"> AFASAK (aspirin vs warfarin standard dose), 1989 </a> <br> </td> <td> aspirin (low dose 75 mg)<br>  <i>versus</i> <br> warfarin standard dose(target INR 2.8-4.2) </td> <td> chronic non rheumatic AF </td> <td> follow-up 2 years<br> n=336/335<br> Parallel groups<br> Open <br> Denmark </td> </tr> <tr> <td> <a href="index.html"> SPAF (aspirin , warfarin eligible arm), 1991 </a> <br> </td> <td> aspirin 325mg/d <br>  <i>versus</i> <br> placebo </td> <td> nonrheumatic atrial fibrillation,warfarin eligible patients </td> <td> follow-up 1.3 years<br> n=206/211<br> Parallel groups<br> Double blind <br> USA </td> </tr> <tr> <td> <a href="index.html"> ACTIVE W, 2006 </a> <br> NCT00243178 </td> <td> clopidogrel (75 mg per day) plus aspirin (75�100 mg per day)<br>  <i>versus</i> <br> oral anticoagulation therapy (target international normalised ratio of 2�0�3�0) </td> <td> Patients with atrial fibrillation plus one or more risk factor for stroke </td> <td> follow-up 1.28 y (median)<br> n=3335/3371<br> Parallel groups<br> open <br> </td> </tr> <tr> <td> <a href="index.html"> PETRO (150mg), 2007 </a> <br> </td> <td> dabigatran 150 mg twice daily (alone or combined with 81- or 325-mg aspirin)<br>  <i>versus</i> <br> warfarin administered to achieve an international normalized ratio of 2 to 3 for </td> <td> patients with AF at high risk for thromboembolic events </td> <td> follow-up 12 weeks<br> n=166/70<br> Factorial plan<br> double blind <br> Denmark, The netehrlands, Sweden, US </td> </tr> <tr> <td> <a href="index.html"> RE-LY (150mg), 2009 </a> <br> NCT00262600 </td> <td> dabigatran 150 mg twice a day<br>  <i>versus</i> <br> warfarin adjusted-dose to a 2.0 to 3.0 INR </td> <td> Patients With Non-Valvular Atrial Fibrillation </td> <td> follow-up 2 y (median)<br> n=6076/6022<br> Parallel groups<br> open (blind assessment) <br> 44 countries </td> </tr> <tr> <td> <a href="index.html"> Weitz (edoxaban phase 2), 0 </a> <br> NCT00504556 </td> <td> Four Fixed Dose Regimens of edoxaban (DU-176b)<br>  <i>versus</i> <br> warfarin </td> <td> Subjects With Non- Valvular Atrial Fibrillation </td> <td> follow-up 3 months<br> n=1146/0<br> Parallel groups<br> double-blind <br> USA, Europe, South and central america, </td> </tr> <tr> <td> <a href="index.html"> ROCKET-AF, 2010 </a> <br> NCT00403767 </td> <td> Rivaroxaban 20mg p.o. once daily<br>  <i>versus</i> <br> Warfarin p.o. once daily titrated to a target INR of 2.5 (range 2.0 to 3.0, inclusive) </td> <td> Subjects With Non-Valvular Atrial Fibrillation </td> <td> follow-up median 1.94 y<br> n=7131/7133<br> Parallel groups<br> double blind <br> 45 countries </td> </tr> <tr> <td> <a href="index.html"> AMADEUS, 2008 </a> <br> NCT00070655 </td> <td> subcutaneous idraparinux 2�5 mg weekly<br>  <i>versus</i> <br> adjusted-dose vitamin K antagonists (target of an international normalised ratio of 2�3) </td> <td> patients with atrial fi brillation at risk for thromboembolism </td> <td> follow-up 10.7 months<br> n=2283/2293<br> Parallel groups<br> open <br> </td> </tr> <tr> <td> <a href="index.html"> ACTIVE A, 2009 </a> <br> NCT00249873 </td> <td> clopidogrel 75 mg daily + aspirin 75-100 mg daily<br>  <i>versus</i> <br> aspirin 75-100 mg daily alone </td> <td> Patients with AF and at least one risk factor for stroke and who are not candidates for warfarin therapy </td> <td> follow-up 3.7 y<br> n=3772/3782<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="index.html"> ENGAGE-AF TIMI 48 High dose, 2013 </a> <br> NCT00781391 </td> <td> edoxaban 60mg once daily<br>  <i>versus</i> <br> warfarin (INR 2-3) </td> <td> AF patients (CHADS2 >=2) </td> <td> follow-up 2.8 years<br> n=7035/7036<br> Parallel groups<br> double blind <br> 46 countries </td> </tr> <tr> <td> <a href="index.html"> RE-LY (110mg), 2009 </a> <br> NCT00262600 </td> <td> dabigatran 110 mg twice a day <br>  <i>versus</i> <br> warfarin adjusted dose to a 2-3 INR </td> <td> Patients With Non-Valvular Atrial Fibrillation </td> <td> follow-up 2 y (median)<br> n=6015/6022<br> Parallel groups<br> open (blind assessment) <br> 44 countries </td> </tr> <tr> <td> <a href="index.html"> ARISTOTLE, 2011 </a> <br> NCT00412984 </td> <td> apixaban 5mg twice daily <br>  <i>versus</i> <br> warfarin adjusted for an INR between 2 and 3 </td> <td> subjects with atrial fibrillation and risk factors for stroke </td> <td> follow-up 1.8 yrs (median)<br> n=9120/9081<br> Parallel groups<br> double blind <br> 39 countries </td> </tr> <tr> <td> <a href="index.html"> AVERROES, 2011 </a> <br> NCT00496769 </td> <td> apixaban 5 mg (or 2.5 mg) twice daily<br>  <i>versus</i> <br> aspirin 81-324 md daily </td> <td> patients with atrial fibrillation who have failed or are unsuitable for vitamin K antagonist treatment </td> <td> follow-up maximum 21 months<br> n=2808/2791<br> Parallel groups<br> double blind <br> 36 countries </td> </tr> <tr> <td> <a href="index.html"> phase 2 apixaban, 0 </a> <br> NCT00787150 </td> <td> apixaban 5 or 2.5 mg twice daily<br>  <i>versus</i> <br> warfarin </td> <td> patient with non valvular AF </td> <td> follow-up 12 weeks<br> n=222/0<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="index.html"> phase 2 YM150, 0 </a> <br> NCT00448214 </td> <td> YM150 ASTELLAS<br>  <i>versus</i> <br> warfarin </td> <td> subjects with non-valvular atrial fibrillation </td> <td> follow-up <br> n=-9/-9<br> Parallel groups<br> open <br> Australia </td> </tr> <tr> <td> <a href="index.html"> phase 2 edoxaban, 0 </a> <br> NCT00806624 </td> <td> edoxaban (DU-176b)<br>  <i>versus</i> <br> warfarin </td> <td> male and female subjects aged 18 to 80 years, inclusive, with non-valvular AF and a CHADS2 Score of at least 1 </td> <td> follow-up <br> n=-9/-9<br> Parallel groups<br> double-blind <br> China </td> </tr> <tr> <td> <a href="index.html"> Lip (phase 2 AZD0837), 2009 </a> <br> NCT00684307 </td> <td> AZD0837 for 3-9 months<br>  <i>versus</i> <br> dose-adjusted Vitamin-K antagonists (VKA) (aiming for an international normalized ratio (INR) 2.0 to 3.0) </td> <td> patients with non-valvular atrial fibrillation (AF) with one or more additional risk factors for stroke </td> <td> follow-up 3 or 9 months<br> n=636/318<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="index.html"> phase 2 AZD0837, 0 </a> <br> NCT00623779 </td> <td> AZD0837<br>  <i>versus</i> <br> aspirin </td> <td> patients with atrial fibrillation, who are appropriate for but unable or unwilling to take Vitamin-K antagonist(VKA) therapy </td> <td> follow-up <br> n=-9/-9<br> Parallel groups<br> open <br> </td> </tr> <tr> <td> <a href="index.html"> phase 2 dabigatran, 0 </a> <br> NCT01136408 </td> <td> Dabigatran 110, 220, 300 mg twice daily<br>  <i>versus</i> <br> warfarin </td> <td> patients with non-valvular atrial fibrillation (paroxysmal, persistent or permanent) </td> <td> follow-up <br> n=-9/-9<br> Parallel groups<br> open <br> Japan </td> </tr> <tr> <td> <a href="index.html"> Japanese AF Trial, 2006 </a> <br> </td> <td> aspirin at 150 to 200 mg per day<br>  <i>versus</i> <br> no antiplatelet or anticoagulant therapy </td> <td> patients with nonvalvular atrial fibrillation </td> <td> follow-up <br> n=426/445<br> <br> <br> </td> </tr> <tr> <td> <a href="index.html"> BAFTA (aspirin vs warfarin standard dose), 0 </a> <br> </td> <td> aspirin (75 mg/d)<br>  <i>versus</i> <br> warfarin standard dose (target INR:2-3) </td> <td> elderly people, primary care setting </td> <td> follow-up <br> n=-9/-9<br> Parallel groups<br> Open <br> England </td> </tr> <tr> <td> <a href="index.html"> idraparinux BOREALIS-AF, 0 </a> <br> NCT00580216 </td> <td> idraparinuxonce-weekly subcutaneous injection<br>  <i>versus</i> <br> warfarin oral INR adjusted-dose </td> <td> </td> <td> follow-up <br> n=-9/-9<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="index.html"> EmbraceAC, </a> <br> </td> <td> tecarfarin<br>  <i>versus</i> <br> warfarin </td> <td> AF, implanted prosthetic heart valves, and a history of venous thromboembolic disease </td> <td> follow-up <br> n=-9/-9<br> <br> <br> </td> </tr> <tr> <td> <a href="index.html"> OPAL-2, </a> <br> NCT00938730 </td> <td> YM150<br>  <i>versus</i> <br> warfarin </td> <td> subjects with non-valvular atrial fibrillation </td> <td> follow-up <br> n=-9/-9<br> <br> double-blind <br> Australia </td> </tr> <tr> <td> <a href="index.html"> ROCKET J, </a> <br> NCT00494871 </td> <td> Rivaroxaban<br>  <i>versus</i> <br> warfarin </td> <td> </td> <td> follow-up <br> n=-9/-9<br> parallel groups<br> double-blind <br> Japan </td> </tr> </table> <h2>References</h2> <p> <b>PATAF (vs coumadin low dose), 1999 : </b> Hellemons BS, Langenberg M, Lodder J, Vermeer F, Schouten HJ, Lemmens T, van Ree JW, Knottnerus JAPrimary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin. <i>BMJ 1999 Oct 9;319:958-64</i> [PMID 10514159] </p> <p> <b>AFASAK II (aspirin vs warfarin low dose), 1998 : </b> Gullov AL, Koefoed BG, Petersen P, Pedersen TS, Andersen ED, Godtfredsen J, Boysen GFixed minidose warfarin and aspirin alone and in combination vs adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study. <i>Arch Intern Med 1998 Jul 27;158:1513-21</i> [PMID 9679792] </p> <p> <b>PATAF (coumadin low dose vs coumadin standard dose), 1999 : </b> Hellemons BS, Langenberg M, Lodder J, Vermeer F, Schouten HJ, Lemmens T, van Ree JW, Knottnerus JAPrimary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin. <i>BMJ 1999 Oct 9;319:958-64</i> [PMID 10514159] </p> <p> <b>AFASAK II (warfarin low dose vs warfarin standard dose), 1998 : </b> Gullov AL, Koefoed BG, Petersen P, Pedersen TS, Andersen ED, Godtfredsen J, Boysen GFixed minidose warfarin and aspirin alone and in combination vs adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study. <i>Arch Intern Med 1998 Jul 27;158:1513-21</i> [PMID 9679792] </p> <p> <b>AFASAK II (warfarin low dose+aspirin vs warfarin standard dose), 1998 : </b> Gullov AL, Koefoed BG, Petersen P, Pedersen TS, Andersen ED, Godtfredsen J, Boysen GFixed minidose warfarin and aspirin alone and in combination vs adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study. <i>Arch Intern Med 1998 Jul 27;158:1513-21</i> [PMID 9679792] </p> <p> <b>SPAF III, 1996 : </b> Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. <i>Lancet. 1996 Sep 7;348(9028):633-8.</i> [PMID 8782752] </p> <p> <b>AFASAK1, 1989 : </b> Petersen P, Boysen G, Godtfredsen J, Andersen ED, Andersen BPlacebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. 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