63. K/DOQI Workgroup. K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis 2005; 45:S1. 64. Bozbas H, Atar I, Yildirir A, et al. Prevalence and predictors of arrhythmia in end stage renal disease patients on hemodialysis. Ren Fail 2007; 29:331. 65. Go AS, Fang MC, Udaltsova N, et al. Impact of proteinuria and glomerular filtration rate on risk of thromboembolism in atrial fibrillation: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study. Circulation 2009; 119:1363. 66. Olesen JB, Lip GY, Kamper AL, et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med 2012; 367:625. 67. Limdi NA, Beasley TM, Baird MF, et al. Kidney function influences warfarin responsiveness and hemorrhagic complications. J Am Soc Nephrol 2009; 20:912. 68. Nakayama M, Metoki H, Terawaki H, et al. Kidney dysfunction as a risk factor for first symptomatic stroke events in a general Japanese population the Ohasama study. Nephrol Dial Transplant 2007; 22:1910. 69. Rold n V, Mar n F, Manzano-Fernandez S, et al. Does chronic kidney disease improve the predictive value of the CHADS2 and CHA2DS2-VASc stroke stratification risk scores for atrial fibrillation? Thromb Haemost 2013; 109:956. 70. Kornej J, Hindricks G, Kosiuk J, et al. Renal dysfunction, stroke risk scores (CHADS2, CHA2DS2-VASc, and R2CHADS2), and the risk of thromboembolic events after catheter ablation of atrial fibrillation: the Leipzig Heart Center AF Ablation Registry. Circ Arrhythm Electrophysiol 2013; 6:868. 71. Ha JT, Neuen BL, Cheng LP, et al. Benefits and Harms of Oral Anticoagulant Therapy in Chronic Kidney Disease: A Systematic Review and Meta-analysis. Ann Intern Med 2019; 171:181. https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 23/41 7/6/23, 12:39 PM Atrial fibrillation in adults: Selection of candidates for anticoagulation - UpToDate 72. Chan KE, Lazarus JM, Thadhani R, Hakim RM. Warfarin use associates with increased risk for stroke in hemodialysis patients with atrial fibrillation. J Am Soc Nephrol 2009; 20:2223. 73. Wizemann V, Tong L, Satayathum S, et al. Atrial fibrillation in hemodialysis patients: clinical features and associations with anticoagulant therapy. Kidney Int 2010; 77:1098. 74. Winkelmayer WC, Liu J, Setoguchi S, Choudhry NK. Effectiveness and safety of warfarin initiation in older hemodialysis patients with incident atrial fibrillation. Clin J Am Soc Nephrol 2011; 6:2662. 75. Shah M, Avgil Tsadok M, Jackevicius CA, et al. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation 2014; 129:1196. 76. Carrero JJ, Evans M, Szummer K, et al. Warfarin, kidney dysfunction, and outcomes following acute myocardial infarction in patients with atrial fibrillation. JAMA 2014; 311:919. 77. Bonde AN, Lip GY, Kamper AL, et al. Net clinical benefit of antithrombotic therapy in patients with atrial fibrillation and chronic kidney disease: a nationwide observational cohort study. J Am Coll Cardiol 2014; 64:2471. 78. Randhawa MS, Vishwanath R, Rai MP, et al. Association Between Use of Warfarin for Atrial Fibrillation and Outcomes Among Patients With End-Stage Renal Disease: A Systematic Review and Meta-analysis. JAMA Netw Open 2020; 3:e202175. 79. ACTIVE Writing Group of the ACTIVE Investigators, Connolly S, Pogue J, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006; 367:1903. 80. ACTIVE Investigators, Connolly SJ, Pogue J, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 2009; 360:2066. 81. Tereshchenko LG, Henrikson CA, Cigarroa J, Steinberg JS. Comparative Effectiveness of Interventions for Stroke Prevention in Atrial Fibrillation: A Network Meta-Analysis. J Am Heart Assoc 2016; 5. 82. Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994; 120:897. 83. Sj lander S, Sj lander A, Svensson PJ, Friberg L. Atrial fibrillation patients do not benefit from acetylsalicylic acid. Europace 2014; 16:631. 84. Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011; 364:806. 85. 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 https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 24/41 7/6/23, 12:39 PM Atrial fibrillation in adults: Selection of candidates for anticoagulation - UpToDate trial. Lancet 1996; 348:633. 86. Gull v AL, Koefoed BG, Petersen P, et al. Fixed 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. Arch Intern Med 1998; 158:1513. 87. Flaker GC, Gruber M, Connolly SJ, et al. Risks and benefits of combining aspirin with anticoagulant therapy in patients with atrial fibrillation: an exploratory analysis of stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) trials. Am Heart J 2006; 152:967. 88. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130:e199. 89. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation 2019; 140:e125. 90. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021; 42:373. Topic 128998 Version 11.0 https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 25/41 7/6/23, 12:39 PM Atrial fibrillation in adults: Selection of candidates for anticoagulation - UpToDate GRAPHICS Comparison of the CHADS and CHA DS -VASc risk stratification scores for 2 patients with nonvalvular AF 2 2 Definition and scores for CHADS and Stroke risk stratification with the 2 CHA DS -VASc CHADS and CHA DS -VASc scores 2 2 2 2 2 Unadjusted ischemic stroke rate [1] CHADS acronym Score CHADS acronym 2 2 (% per year) Congestive HF 1 0 0.6 Hypertension 1 1 3.0 Age 75 years 1 2 4.2 Diabetes mellitus 1 3 7.1 Stroke/TIA/TE 2 4 11.1 Maximum score 6 5 12.5 6 13.0 Unadjusted ischemic stroke rate CHA DS -VASc 2 2 [2] CHA DS -VASc acronym Score 2 2 acronym (% per year) Congestive HF 1 0 0.2 Hypertension 1 1 0.6 Age 75 years 2 2 2.2 Diabetes mellitus 1 3 3.2 Stroke/TIA/TE 2 4 4.8 Vascular disease (prior MI, PAD, or 1 5 7.2 aortic plaque) Age 65 to 74 years 1 6 9.7 Sex category (ie, female sex) 1 7 11.2 Maximum score 9 8 10.8 9 12.2 AF: atrial fibrillation; CHADS : Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, prior Stroke or TIA or thromboembolism (doubled); CHA DS -VASc: Congestive heart failure, Hypertension, Age 75 years (doubled), Diabetes mellitus, prior Stroke or TIA or thromboembolism 2 2 2 https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 26/41 7/6/23, 12:39 PM Atrial fibrillation in adults: Selection of candidates for anticoagulation - UpToDate (doubled), Vascular disease, Age 65 to 74 years, Sex category; HF: heart failure; TIA: transient ischemic attack; TE: thromboembolism; MI: myocardial infarction; PAD: peripheral artery disease. [3] These unadjusted (not adjusted for possible use of aspirin) stroke rates were published in 2012 . Actual rates of stroke in contemporary cohorts might vary from these estimates. References: 1. Gage BF, Waterman AD, Shannon W, et al. Validation of clinical classi cation schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001; 285:2864. 2. Lip GYH, Nieuwlaat R, Pisters R, et al. Re ning clinical risk strati cation for predicting stroke and thromboembolism in atrial brillation using a novel risk factor-based approach: the euro heart survey on atrial brillation. Chest 2010; 137:263. 3. Friberg L, Rosenqvist M, Lip GY. Evaluation of risk strati cation schemes for ischaemic stroke and bleeding in 182 678 patients with atrial brillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J 2012; 33:1500. Original table and unadjusted ischemic stroke rates, as noted above, have been modi ed for this publication. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014; 64:e1. Table used with the permission of Elsevier Inc. All rights reserved. Graphic 94752 Version 14.0 https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 27/41 7/6/23, 12:39 PM Atrial fibrillation in adults: Selection of candidates for anticoagulation - UpToDate Possible contraindications to anticoagulation Possible contraindication Factors to consider Active, clinically significant Site and degree of bleeding (eg, nosebleeds and menses generally bleeding are not a contraindication; active intracerebral bleeding is almost always an absolute contraindication), interval since bleeding stopped Severe bleeding diathesis Nature, severity, and reversibility of bleeding diathesis Severe thrombocytopenia (platelet count <50,000/microL) Absolute platelet count, platelet count trend, and platelet function (eg, some individuals with ITP and a platelet count in the range of 30,000 to 50,000 may tolerate anticoagulation if needed) Major trauma Site and extent of trauma, time interval since event (eg, for a patient with a mechanical heart valve it may be appropriate to anticoagulate sooner after trauma than a patient with a lesser indication) Invasive procedure or obstetric delivery (recent, emergency, or planned) Type of procedure and associated bleeding risk, interval between procedure and anticoagulation Previous intracranial hemorrhage Time interval since hemorrhage and underlying cause (eg, trauma or uncontrolled hypertension) Intracranial or spinal tumor Site and type of tumor, other comorbidities Neuraxial anesthesia Interval since spinal/epidural puncture or catheter removal, other alternatives for anesthesia; traumatic procedures are more concerning Severe, uncontrolled hypertension Absolute blood pressure and blood pressure trend This list does not take the place of clinical judgment in deciding whether or not to administer an anticoagulant. In any patient, the risk of bleeding from an anticoagulant must be weighed against the risk of thrombosis and its consequences. The greater the thromboembolic risk, the greater the tolerance for the possibility of bleeding and for shortening the time interval between an episode of bleeding and anticoagulant initiation. Refer to UpToDate content on the specific indication for the anticoagulant and the specific possible contraindication for discussions of these risks. ITP: immune thrombocytopenia. Graphic 107527 Version 4.0 https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 28/41 7/6/23, 12:39 PM Atrial fibrillation in adults: Selection of candidates for anticoagulation - UpToDate Clinical characteristics comprising the HAS-BLED bleeding risk score Letter Clinical characteristic* Points H Hypertension (ie, uncontrolled blood pressure) 1 A Abnormal renal and liver function (1 point each) 1 or 2 S Stroke 1 B Bleeding tendency or predisposition 1 L Labile INRs (for patients taking warfarin) 1 E Elderly (age greater than 65 years) 1 D Drugs (concomitant aspirin or NSAIDs) or excess alcohol use (1 point each) 1 or 2 Maximum 9 points HAS-BLED score (total points) Bleeds per 100 patient-years 0 1.13 1 1.02 2 1.88 3 3.74 4 8.70 5 to 9 Insufficient data The HAS-BLED bleeding risk score has only been validated in patients with atrial fibrillation receiving warfarin. Refer to UpToDate topics on anticoagulation in patients with atrial fibrillation and on specific anticoagulants for further information and other bleeding risk scores and their performance relative to clinical judgment. INR: international normalized ratio; NSAIDs: nonsteroidal antiinflammatory drugs. Hypertension is defined as systolic blood pressure >160 mmHg. Abnormal renal function is defined as the presence of chronic dialysis, renal transplantation, or serum creatinine 200 micromol/L. Abnormal liver function is defined as chronic hepatic disease (eg, cirrhosis) or biochemical evidence of significant hepatic derangement (eg, bilirubin more than 2 times the upper limit of normal, plus 1 or more of aspartate transaminase, alanine transaminase, and/or alkaline phosphatase more than 3 times the upper limit of normal). Bleeding predisposition includes chronic bleeding disorder or https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 29/41 7/6/23, 12:39 PM Atrial fibrillation in adults: Selection of candidates for anticoagulation - UpToDate previous bleeding requiring hospitalization or transfusion. Labile INRs for a patient on warfarin include unstable INRs, excessively high INRs, or <60% time in therapeutic range. Based on initial validation cohort from Pisters R. A novel-user-friendly score (HAS-BLED) to assess 1- year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138:1093. Actual rates of bleeding in contemporary cohorts may vary from these estimates. Original gure modi ed for this publication. Lip GY. Implications of the CHA2DS2-VASc and HAS-BLED Scores for thromboprophylaxis in atrial brillation. Am J Med 2011; 124:111. Table used with the permission of Elsevier Inc. All rights reserved. Graphic 75259 Version 16.0 https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 30/41 7/6/23, 12:39 PM Atrial fibrillation in adults: Selection of candidates for anticoagulation - UpToDate Benefit of warfarin in chronic atrial fibrillation Efficacy of anticoagulation with warfarin to prevent ischemic stroke and other thromboemboli in 4 major studies. An intention to treat approach was used, and transient ischemic attack and hemorrhage were excluded. The numbers at the top represent the risk reduction with warfarin therapy, which ranged from 45 to 82%. SPAF: Stroke Prevention in Atrial Fibrillation; AFASAK: Copenhagen AFASAK Study; BAATAF: Boston Area Anticoagulation Trial for Atrial Fibrillation; CAFA: Canadian Atrial Fibrillation Anticoagulation Study. The data in the warfarin group in the SPAF assumes that half of the events were attributable to warfarin toxicity. Data from: Connolly SJ, Laupacis AN, Gent M, et al. Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. J Am Coll Cardiol 1991; 18:349. Graphic 79839 Version 4.0 https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 31/41 7/6/23, 12:39 PM Atrial fibrillation in adults: Selection of candidates for anticoagulation - UpToDate Trials comparing direct oral anticoagulants versus warfarin in atrial fibrillation Baseline characteristics Trial details of trial participants Trial N Percent Mean CHADS score Study drug (DOAC) and dose 2 on aspirin Compariso RE-LY 18,113 2.1 40% Dabigatran 110 mg twice Warfarin (target IN daily or 150 mg twice daily 3.0) ROCKET- 14,264 3.5 36% Rivaroxaban 20 mg once Warfarin (target IN AF daily* 3.0) ARISTOTLE 18,201 2.1 31% Apixaban 5 mg twice daily Warfarin (target IN 3.0) ENGAGE AF-TIMI 48 21,105 2.8 29% Edoxaban 30 mg once daily or 60 mg once daily Warfarin (target IN 3.0) Event rates for key outcomes Stroke or systemic Death Hemorrhagic s embolic event Trial Relative effect (95% CI) Relative effect (95% CI) DOAC Warfarin DOAC Warfarin DOAC Warfarin RE-LY 110 3.75 4.13 RR 0.91 1.53 1.69 RR 0.91 0.12 0.38 mg (0.8- 1.03) (0.74- 1.11) 150 3.64 4.13 RR 0.88 1.11 1.69 RR 0.66 0.10 0.38 mg (0.77- (0.53- 1.00) 0.82) ROCKET-AF 4.5 4.9 HR 0.92 (0.82- 2.1 2.4 HR 0.88 (0.75- 0.26 0.44 1.03) 1.03) ARISTOTLE 3.52 3.94 HR 0.89 (0.80- 1.27 1.60 HR 0.79 (0.66- 0.24 0.47 0.998) 0.95) ENGAGE 30 mg 3.80 4.35 HR 0.87 2.04 1.80 HR 1.13 0.16 0.47 AF-TIMI 48 (0.79- 0.96) (0.96- 1.34) https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 32/41 7/6/23, 12:39 PM Atrial fibrillation in adults: Selection of candidates for anticoagulation - UpToDate ENGAGE AF-TIMI 48 60 mg 3.99 4.35 HR 0.92 (0.83- 1.57 1.80 HR 0.87 (0.73- 0.26 0.47 1.01) 1.04) Combined results 6.90 7.68 RR 0.90 (0.85- 3.11 3.79 RR 0.81 (0.73- 0.44 0.90 0.95) 0.91) DOAC: direct oral anticoagulant; AF: atrial fibrillation; N: number of trial participants; CHADS : score 2 to estimate risk of stroke with 1 point assigned for each of the following clinical features: history of congestive heart failure, hypertension, age 75 years, or diabetes mellitus, and 2 points assigned for prior stroke or transient ischemic attack; INR: international normalized ratio; HR: hazard ratio; RR: relative risk. Dose of rivaroxaban was adjusted to 15 mg once daily for renal insufficiency (creatinine clearance 30 to 49 mL/minute [0.5 to 0.82 mL/second]). Dose of apixaban was adjusted to 2.5 mg twice daily for patients with two or more of: age 80 years, body weight 60 kg, or renal insufficiency (serum creatinine level 1.5 mg/dL [133 micromol/L]). For patients in either dose group, the dose of edoxaban was reduced by 50% if any of the following characteristics were present: estimated creatinine clearance 30 to 50 mL/minute, body weight 60 kg, or concomitant use of verapamil, quinidine, or dronedarone. For the individual trials, the annual event rate (expressed as %/year) is presented for each outcome. For the meta-analysis, the table provides the absolute event rates (%) during the total study duration, which varied between studies (median follow-up 1.8 to 2.8 years). Major bleeding was variably defined. In RE-LY, it was defined as a reduction in hemoglobin of at least 2 g/dL [20 g/L], transfusion of 2 units of blood, or symptomatic bleeding in a critical area or organ. In ROCKET-AF, ARISTOTLE, and ENGAGE AF-TIMI 48, it was defined as fatal bleeding, bleeding at a critical site, or overt bleeding plus fall in hemoglobin of at least 2 g/dL [20 g/L] or transfusion of 2 units of blood. For ROCKET-AF, the results for hemorrhagic stroke and for bleeding are based on an as-treated safety population. These combined results include data for dabigatran 150 mg twice daily, rivaroxaban 20 mg once daily, apixaban 5 mg twice daily, and edoxaban 60 mg once daily. Data from: 1. Connolly SJ, Ezekowitz MD, Eikelbloom YS, et al. Dabigatran versus warfarin in patients with atrial brillation; N Engl J Med 2009; 361:1139. 2. Patel MR, Maha ey KE, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial brillation; N Engl J Med 2011; 365:883. 3. Granger CB, Alexander JH, McMurray JJV, et al. Apixaban versus warfarin in patients with atrial brillation; N Engl J Med 2011; 365:981. 4. Giugliano RP, Ru CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial brillation. N Engl J Med 2013; 369:2093. https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 33/41 7/6/23, 12:39 PM Atrial fibrillation in adults: Selection of candidates for anticoagulation - UpToDate 5. Ru CT, Giugliano RP, Braunwald E, et al. Comparison of the e cacy and safety of new oral anticoagulants with warfarin in patients with atrial brillation: a meta-analysis of randomised trials. Lancet 2014; 383:955. Graphic 131871 Version 2.0 https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 34/41 7/6/23, 12:39 PM Atrial fibrillation in adults: Selection of candidates for anticoagulation - UpToDate ATRIA stroke risk model point scoring system Points without prior Risk factor Points with prior stroke stroke Age, y 85 6 9 75 to 84 5 7 65 to 74 3 7 <65 0 8 Female 1 1 Diabetes 1 1 CHF 1 1 Hypertension 1 1 Proteinuria 1 1 eGFR <45 or ESRD 1 1 Possible point scores range from 0 to 12 for those without a prior stroke and from 7 to 15 for those with a prior stroke. ATRIA: Anticoagulation and Risk Factors in Atrial Fibrillation; CHF: congestive heart failure; eGFR: estimated glomerular filtration rate; ESRD: end-stage renal disease. Reprinted with permission. J Am Heart Assoc 2013; 2:e000250. Copyright 2013 American Heart Association, Inc. Graphic 90032 Version 1.0 https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 35/41 7/6/23, 12:39 PM Atrial fibrillation in adults: Selection of candidates for anticoagulation - UpToDate Staging of patients who meet the definition of CKD GFR and albuminuria grid to reflect the risk of progression by intensity of coloring (green, yellow, orange, red, deep red). The numbers in the boxes are a guide to the frequency of monitoring (number of times per year). GFR: glomerular filtration rate. Reprinted by permission from: Macmillan Publishers Ltd: Kidney International. KDIGO. Summary of recommendation statements. Kidney Int 2013; 3(Suppl):5. Copyright 2013. http://www.nature.com/ki/index.html. Graphic 59716 Version 7.0 https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 36/41 7/6/23, 12:39 PM Atrial fibrillation in adults: Selection of candidates for anticoagulation - UpToDate Prevalence of atrial fibrillation in chronic kidney disease patients The prevalence (percent) of atrial fibrillation in the general population and different cohorts of patients with CKD are shown: While patients with peritoneal dialysis appear to suffer less frequently from atrial fibrillation, in those on hemodialysis, the prevalence was observed to be 10- to 20-fold higher than in the general population. Age was in all groups a key factor. CKD: chronic kidney disease. Reproduced with permission from: Reinecke H, Brand E, Mesters R, et al. Dilemmas in the management of atrial brillation in chronic kidney disease. J Am Soc Nephrol 2009; 20:705. Copyright 2009 American Society of Nephrology. Graphic 55373 Version 6.0 https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 37/41 7/6/23, 12:39 PM Atrial fibrillation in adults: Selection of candidates for anticoagulation - UpToDate Meta-analysis of randomized controlled trials of warfarin and aspirin for primary prevention of stroke in atrial fibrillation Stroke Major bleeding Comparison Odds ratio, p Odds ratio, 95 p 95% CI value percent CI value Conventional dose warfarin versus placebo 0.31 (0.19 to 0.50) <0.001 1.88 (0.88 to 4.0) 0.10 Aspirin versus placebo 0.68 (0.46 to 0.06 0.82 (0.37 to 1.78) >0.2 1.02) Conventional dose warfarin versus aspirin 0.66 (0.45 to 0.04 1.61 (0.75 to 3.44) >0.2 0.99) Conventional dose warfarin versus low dose warfarin 0.52 (0.25 to 1.08) 0.08 2.21 (0.67 to 7.25) 0.19 Conventional dose warfarin versus low dose warfarin plus aspirin 0.44 (0.14 to 1.39) 0.16 1.14 (0.55 to 2.36) >0.2 Low dose warfarin versus aspirin 1.01 (0.49 to 2.06) >0.2 1.04 (0.43 to 2.48) >0.2 NOTE: The data in this table cannot be directly applied to clinical practice (an individual patient) since the decision to use warfarin or aspirin is importantly related to a patient's estimated risk of embolic events. Adapted from McNamara RL, Tamariz LJ, Segal JB, Bass EB. Ann Intern Med 2004; 139:1018. Graphic 66736 Version 2.0 https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 38/41 7/6/23, 12:39 PM Atrial fibrillation in adults: Selection of candidates for anticoagulation - UpToDate Low-dose warfarin plus aspirin is not optimal in high-risk AF Cumulative event rate of patients with AF at high risk for thromboembolism in the SPAF III trial. High risk was defined as the presence of at least 1 of the following: previous thromboembolism, female older than 75 years of age, heart failure or severe left ventricular systolic dysfunction, and systolic pressure >160 mmHg. There was a much lower incidence of events with standard adjusted- dose warfarin therapy (INR 2 to 3) compared with treatment with aspirin and low-dose warfarin (INR 1.2 to 1.5; p<0.0001). AF: atrial fibrillation; INR: international normalized ratio. Data from Stroke Prevention in Atrial Fibrillation Investigators. Lancet 1996; 348:633. Graphic 72790 Version 3.0 https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 39/41 7/6/23, 12:39 PM Atrial fibrillation in adults: Selection of candidates for anticoagulation - UpToDate Increased stroke risk with low-dose warfarin plus aspirin in AF Results from the SPAF III trial of high-risk patients showing significantly higher event rates for intracranial hemorrhage and ischemic stroke in patients treated with fixed low-dose warfarin plus aspirin compared with standard adjusted-dose warfarin. The risk was greater in those with a previous thromboembolic event. AF: atrial fibrillation. Data from Stroke Prevention in Atrial Fibrillation Investigators. Lancet 1996; 348:633. Graphic 62833 Version 2.0 https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 40/41 7/6/23, 12:39 PM Atrial fibrillation in adults: Selection of candidates for anticoagulation - UpToDate Contributor Disclosures Warren J Manning, MD Equity Ownership/Stock Options: Pfizer [Anticoagulants]. All of the relevant financial relationships listed have been mitigated. Daniel E Singer, MD Grant/Research/Clinical Trial Support: Bristol-Myers Squibb [Screening for atrial fibrillation]. Consultant/Advisory Boards: Bristol-Myers Squibb [Atrial fibrillation and stroke]; Fitbit [Screening for atrial fibrillation]; Medtronic [Atrial fibrillation and stroke]. All of the relevant financial relationships listed have been mitigated. Gregory YH Lip, MD, FRCPE, FESC, FACC Consultant/Advisory Boards: BMS/Pfizer [Atrial fibrillation and thrombosis]; Boehringer Ingelheim [Atrial fibrillation and thrombosis]; Daiichi-Sankyo [Atrial fibrillation and thrombosis]. Speaker's Bureau: BMS/Pfizer [Atrial fibrillation and thrombosis]; Boehringer Ingelheim [Atrial fibrillation and thrombosis]; Daiichi-Sankyo [Atrial fibrillation and thrombosis]. All of the relevant financial relationships listed have been mitigated. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Scott E Kasner, MD Grant/Research/Clinical Trial Support: Bayer [Stroke]; Bristol Meyers Squibb [Stroke]; Medtronic [Stroke]; WL Gore and Associates [Stroke]. Consultant/Advisory Boards: Abbvie [Stroke]; AstraZeneca [Stroke]; BMS [Stroke]; Diamedica [Stroke]; Medtronic [Stroke]. All of the relevant financial relationships listed have been mitigated. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/atrial-fibrillation-in-adults-selection-of-candidates-for-anticoagulation/print 41/41