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Background: Studies evaluating the effects of atrial fibrillation (AF) catheter ablation versus antiarrhythmic therapy on outcomes have shown mixed results. In addition, guidelines recommend continuing oral anticoagulation (OAC) after ablation for those at risk of stroke, but real-world data are lacking., Methods: We evaluated outcomes including death, myocardial infarction, stroke or systemic embolism, intracranial bleeding, major bleeding, and hospitalization in patients undergoing AF ablation compared with a propensity score matched cohort of patients treated with anti-arrhythmic medications only in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation registries. Cox proportional hazards regression was performed to evaluate the association between AF ablation and outcomes. We then evaluated patterns of treatment with OAC among AF ablation patients., Results: Among 21 595 patients, 1190 (6%) underwent de novo AF ablation. Our propensity score-matched cohort included 1087 patients who underwent AF ablation matched 1:1 with 1087 patients treated with antiarrhythmic medications only. There were no significant differences in the risk of all-cause and cardiovascular death, and most other major adverse cardiovascular and neurological events. AF catheter ablation was associated with an increased risk of all-cause hospitalization during follow-up (hazard ratio, 1.24 [95% CI, 1.05-1.46]), particularly in the first 3 months (the standard blanking period) after the procedure. Among those who underwent AF ablation with a CHA 2 DS 2 VASc score ≥2 for men and ≥3 for women, 23% had OAC discontinued after ablation. Among those who discontinued OAC, the median time to discontinuation was 6.2 months., Conclusions: In this large US national registry, we found no difference in adjusted rates of cardiovascular or all-cause death between patients treated with AF catheter ablation and antiarrhythmic medications only. Notably, discontinuation of OAC after ablation remains relatively common despite guideline recommendations for continued stroke prevention therapy in patients at risk of stroke.

Background: Few studies describe both inpatient and outpatient treatment and outcomes of patients with acute venous thromboembolism in the United States., Methods: A multi-institutional cohort of patients diagnosed with confirmed pulmonary embolism or deep venous thrombosis during the years 2004 through 2010 was established from 4 large, US-based integrated health care delivery systems. Computerized databases were accessed and medical records reviewed to collect information on patient demographics, clinical risk factors, initial antithrombotic treatment, and vital status. Multivariable Cox regression models were used to estimate the risk of death at 90 days., Results: The cohort comprised 5497 adults with acute venous thromboembolism. Pulmonary embolism was predominantly managed in the hospital setting (95.0%), while 54.5% of patients with lower extremity thrombosis were treated as outpatients. Anticoagulant treatment differed according to thromboembolism type: 2688 patients (92.8%) with pulmonary embolism and 1625 patients (86.9%) with lower extremity thrombosis were discharged on anticoagulants, compared with 286 patients (80.1%) with upper extremity thrombosis and 69 (54.8%) patients with other thrombosis. While 4.5% of patients died during the index episode, 15.4% died within 90 days. Pulmonary embolism was associated with a higher 90-day death risk than lower extremity thrombosis (adjusted hazard ratio 1.23; 95% confidence interval, 1.04-1.47), as was not being discharged on anticoagulants (adjusted hazard ratio 5.56; 95% confidence interval, 4.76-6.67)., Conclusions: In this multicenter, community-based study of patients with acute venous thromboembolism, anticoagulant treatment and outcomes varied by thromboembolism type. Although case fatality during the acute episode was relatively low, 15.4% of people with thromboembolism died within 90 days of the index diagnosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Treatment patterns and outcomes of individuals with vascular disease who have new-onset atrial fibrillation (AF) are not well characterized., Methods: Among patients with new-onset AF, we analyzed treatment and outcomes in those with or without vascular disease in the ORBIT-AF II registry. Vascular disease was defined as coronary disease with or without myocardial infarction (MI) or revascularization, or peripheral artery disease. The primary outcomes included major adverse cardiovascular or neurological events (MACNE) and major bleeding. Cox proportional hazard models were used to adjust the difference in patient characteristics., Results: Overall 1920 of 6203 (31.0%) of new-onset AF had vascular disease. In patients with vascular disease, 62.2% of those were treated with direct oral anticoagulants (DOACs) and 23.4% with warfarin. Dual therapy and triple therapy were used in 36.9% and 4.9%, respectively. Vascular disease patients had increased risk of MACNE (adjusted hazard ratio [aHR] 1.83 [95%CIs 1.32-2.55]), but not major bleeding (aHR 1.24 [0.95-1.63]). Among patients with vascular disease, relative to those on warfarin, those treated with DOACs had similar risk for MACNE (aHR 1.20 [0.77-1.87]) but lower risks for bleeding, although it did not reach statistical significance (aHR 0.70 [0.43-1.15]). Concomitant antiplatelet therapy was associated with higher bleeding (aHR 2.27 [1.38-3.73]) with no apparent reduction in MACNE (aHR 1.50 [1.00-2.25])., Conclusions: Most patients with AF and vascular disease were managed with oral anticoagulation. About half of them were also treated with concomitant antiplatelet therapy, which was associated with increased risk of bleeding, without evidence of improved cardiovascular outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background Patient satisfaction with therapy is an important metric of care quality and has been associated with greater medication persistence. We evaluated the association of patient satisfaction with warfarin therapy to other metrics of anticoagulation care quality and clinical outcomes among patients with atrial fibrillation ( AF ). Methods and Results Using data from the ORBIT - AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry, patients were identified with AF who were taking warfarin and had completed an Anti-Clot Treatment Scale ( ACTS ) questionnaire, a validated metric of patient-reported burden and benefit of oral anticoagulation. Multivariate regressions were used to determine association of ACTS burden and benefit scores with time in therapeutic international normalized ratio range ( TTR ; both ≥75% and ≥60%), warfarin discontinuation, and clinical outcomes (death, stroke, major bleed, and all-cause hospitalization). Among 1514 patients with AF on warfarin therapy (75±10 years; 42% women; CHA 2 DS 2 - VAS c 3.9±1.7), those most burdened with warfarin therapy were younger and more likely to be women, have paroxysmal AF , and to be treated with antiarrhythmic drugs. After adjustment for covariates, ACTS burden scores were independent of TTR ( TTR ≥75%: odds ratio, 1.01 [95% CI , 0.99-1.03]; TTR ≥60%: odds ratio, 1.01 [95% CI , 0.98-1.05]), warfarin discontinuation (odds ratio, 0.99; 95% CI , 0.97-1.01), or clinical outcomes. ACTS benefit scores were also not associated with TTR , warfarin discontinuation, or clinical outcomes. Conclusions In a large registry of patients with AF taking warfarin, ACTS scores provided independent information beyond other traditional metrics of oral anticoagulation care quality and identified patient groups at high risk for dissatisfaction with warfarin therapy.

Background: Stroke rates in patients with nonvalvular atrial fibrillation (AF) who are not receiving anticoagulant therapy vary widely across published studies; the resulting effect on the net clinical benefit of anticoagulation in AF is unknown., Objective: To determine the effect of variation in published AF stroke rates on the net clinical benefit of anticoagulation., Design: Markov model decision analysis. Warfarin was the base case, and non-vitamin K antagonist oral anticoagulants (NOACs) were modeled in a secondary analysis., Setting: Community-dwelling adults., Patients: 33 434 adults with incident AF., Measurements: Quality-adjusted life-years (QALYs)., Results: Of the 33 434 patients, 27 179 had a CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes, stroke, and vascular disease) score of 2 or more. The population benefit of warfarin anticoagulation for these patients was least using stroke rates from the ATRIA (AnTicoagulation and Risk Factors In Atrial Fibrillation) study and greatest using those from the Danish National Patient Registry (6290 QALYs [95% CI, ±2.3%] vs. 24 110 QALYs [CI, ±1.9%]; P < 0.001). The optimal CHA2DS2-VASc score threshold for anticoagulation was 3 or more using stroke rates from ATRIA, 2 or more using those from the Swedish AF cohort study, 1 or more using those from the SPORTIF (Stroke Prevention using ORal Thrombin Inhibitor in atrial Fibrillation) study, and 0 or more using those from the Danish National Patient Registry. Accounting for lower rates of NOAC-associated intracranial hemorrhage decreased optimal CHA2DS2-VASc score thresholds, but these thresholds still varied widely., Limitation: Measured benefit may not generalize to other populations., Conclusion: Variation in published AF stroke rates for patients not receiving anticoagulant therapy results in multifold variation in the net clinical benefit of anticoagulation. Guidelines should better reflect the uncertainty in current thresholds of stroke risk score for recommending anticoagulation., Primary Funding Source: None.

Background: Bleeding is commonly cited as a reason for stopping oral anticoagulants (OACs). Whether minor bleeding events (nuisance bleeding, NB) in patients with atrial fibrillation on OACs are associated with OAC discontinuation, major bleeding, and stroke/systemic embolism (SSE) is unknown., Methods: Within the ORBIT-AF prospective, outpatient registry (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation), we identified 6771 patients ≥18 years of age at 172 sites with atrial fibrillation and eligible follow-up visits. NB was ascertained from the medical record and was defined as minor bleeding that did not require medical attention (eg, bruising, hemorrhoidal bleeding). We used multivariable pooled logistic regression modeling to evaluate the associations between NB and major bleeding and SSE in the 180 days after documentation of NB. Our unit of analysis was the patient visit, occurring at ≈6-month intervals for a median of 1.5 years following enrollment. Changes in anticoagulation treatment satisfaction after NB were examined descriptively in a subset of patients., Results: The median age of the overall population was 75.0 (interquartile range, 67.0-81.0); 90.0% were white and 42.5% were female. Among 6771 patients (18 560 visits), n=1357 (20.0%) had documented NB, for an incidence rate of 14.8 events per 100 person-years. Over 96.4% of patients remained on OAC therapy after the NB event. Overall, 287 (4.3%) patients experienced major bleeding and 64 (0.96%) had a SSE event during follow-up. NB was not associated with a significant increased risk of major bleeding over 6 months in models adjusting for the ATRIA bleeding score (Anticoagulation and Risk Factors in Atrial Fibrillation) (odds ratio, 1.04; 95% confidence interval, 0.68-1.60; P=0.86). NB was also not associated with increased SSE risk over 6 months in models adjusting for the CHA 2 DS 2 -VASc risk score (odds ratio, 1.24; 95% confidence interval, 0.53-2.91; P=0.62)., Conclusions: NB is common among patients with atrial fibrillation on OACs. However, NB was not associated with a higher risk of major bleeding or SSE over the next 6 months, suggesting its occurrence should not lead to changes in anticoagulation treatment strategies in OAC-treated patients., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01165710.

Background Current American College of Cardiology/American Heart Association guidelines suggest that for patients with atrial fibrillation who are at low risk for stroke (CHA 2 DS 2 VASc=1) (or women with CHA 2 DS 2 VASc=2) a variety of treatment strategies may be considered. However, in clinical practice, patterns of treatment in these "low-risk" patients are not well described. The objective of this analysis is to define thromboembolic event rates and to describe treatment patterns in patients with low-risk CHA 2 DS 2 VASc scores. Methods and Results We compared characteristics, treatment strategies, and outcomes among patients with a CHA 2 DS 2 VASc=0, CHA 2 DS 2 VASc=1, females with a CHA 2 DS 2 VASc=2, and CHA 2 DS 2 VASc ≥2 in ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) I & II. Compared with CHA 2 DS 2 VASc ≥2 patients (84.2%), those with a CHA 2 DS 2 VASc=0 (60.3%), 1 (69.9%), and females with a CHA 2 DS 2 VASc score=2 (72.4%) were significantly less often treated with oral anticoagulation ( P<0.0001). Stroke rates were low overall and ranged from 0 per 100 patient-years in those with CHA 2 DS 2 VASc=0, 0.8 (95% confidence interval [CI] [0.5-1.2]) in those with CHA 2 DS 2 VASc=1, 0.8 (95% CI [0.4-1.6]) in females with a CHA 2 DS 2 VASc score=2, and 1.7 (95% CI [1.6-1.9]) in CHA 2 DS 2 VASc ≥2. All-cause mortality (per 100 patient-years) was highest in females with a CHA 2 DS 2 VASc score=2 (1.4) (95% CI [0.8-2.3]), compared with patients with a CHA 2 DS 2 VASc=0 (0.2) (95% CI [0.1-1.0]), and CHA 2 DS 2 VASc=1 (1.0) (95% CI [0.7-1.4]), but lower than patients with a CHA 2 DS 2 VASc ≥2 (5.7) (95% CI [5.4-6.0]). Conclusion The majority of CHA 2 DS 2 VASc=0-1 patients are treated with oral anticoagulation. In addition, the absolute risks of death and stroke/transient ischemic attack were low among both male and females CHA 2 DS 2 VASc=0-1 as well as among females with a CHA 2 DS 2 VASc score=2. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01701817.

Introduction: Many patients with atrial fibrillation or atrial flutter (AF/FL) who are high risk for ischemic stroke are not receiving evidence-based thromboprophylaxis. We examined anticoagulant prescribing within 30 days of receiving dysrhythmia care for non-valvular AF/FL in the emergency department (ED)., Methods: This prospective study included non-anticoagulated adults at high risk for ischemic stroke (ATRIA score ≥7) who received emergency AF/FL care and were discharged home from seven community EDs between May 2011 and August 2012. We characterized oral anticoagulant prescribing patterns and identified predictors of receiving anticoagulants within 30 days of the index ED visit. We also describe documented reasons for withholding anticoagulation., Results: Of 312 eligible patients, 128 (41.0%) were prescribed anticoagulation at ED discharge or within 30 days. Independent predictors of anticoagulation included age (adjusted odds ratio [aOR] 0.89 per year, 95% confidence interval [CI] 0.82-0.96); ED cardiology consultation (aOR 1.89, 95% CI [1.10-3.23]); and failure of sinus restoration by time of ED discharge (aOR 2.65, 95% CI [1.35-5.21]). Reasons for withholding anticoagulation at ED discharge were documented in 139 of 227 cases (61.2%), the most common of which were deferring the shared decision-making process to the patient's outpatient provider, perceived bleeding risk, patient refusal, and restoration of sinus rhythm., Conclusion: Approximately 40% of non-anticoagulated AF/FL patients at high risk for stroke who presented for emergency dysrhythmia care were prescribed anticoagulation within 30 days. Physicians were less likely to anticoagulate older patients and those with ED sinus restoration. Opportunities exist to improve rates of thromboprophylaxis in this high-risk population., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. No author has professional or financial relationships with any companies that are relevant to this study. This work was supported by a grant from the Garfield Memorial National Research Fund, with additional support from The Permanente Medical Group Delivery Science Program (via the Physician Researcher Program).

Background: Dabigatran (150 mg twice daily) has been associated with lower rates of stroke than warfarin in trials of atrial fibrillation, but large-scale evaluations in clinical practice are limited., Objective: To compare incidence of stroke, bleeding, and myocardial infarction in patients receiving dabigatran versus warfarin in practice., Design: Retrospective cohort., Setting: National U.S. Food and Drug Administration Sentinel network., Patients: Adults with atrial fibrillation initiating dabigatran or warfarin therapy between November 2010 and May 2014., Measurements: Ischemic stroke, intracranial hemorrhage, extracranial bleeding, and myocardial infarction identified from hospital claims among propensity score-matched patients starting treatment with dabigatran or warfarin., Results: Among 25 289 patients starting dabigatran therapy and 25 289 propensity score-matched patients starting warfarin therapy, those receiving dabigatran did not have significantly different rates of ischemic stroke (0.80 vs. 0.94 events per 100 person-years; hazard ratio [HR], 0.92 [95% CI, 0.65 to 1.28]) or extracranial hemorrhage (2.12 vs. 2.63 events per 100 person-years; HR, 0.89 [CI, 0.72 to 1.09]) but were less likely to have intracranial bleeding (0.39 vs. 0.77 events per 100 person-years; HR, 0.51 [CI, 0.33 to 0.79]) and more likely to have myocardial infarction (0.77 vs. 0.43 events per 100 person-years; HR, 1.88 [CI, 1.22 to 2.90]). However, the strength and significance of the association between dabigatran use and myocardial infarction varied in sensitivity analyses and by exposure definition (HR range, 1.13 [CI, 0.78 to 1.64] to 1.43 [CI, 0.99 to 2.08]). Older patients and those with kidney disease had higher gastrointestinal bleeding rates with dabigatran., Limitation: Inability to examine outcomes by dabigatran dose (unacceptable covariate balance between matched patients) or quality of warfarin anticoagulation (few patients receiving warfarin had available international normalized ratio values)., Conclusion: In matched adults with atrial fibrillation treated in practice, the incidences of stroke and bleeding with dabigatran versus warfarin were consistent with those seen in trials. The possible relationship between dabigatran and myocardial infarction warrants further investigation., Primary Funding Source: U.S. Food and Drug Administration.

Background: Oral anticoagulation (OAC) therapy is associated with increased periprocedural risks after cardiac implantable electronic device (CIED) implantation. Patterns of anticoagulation management involving non-vitamin K antagonist oral anticoagulants (NOACs) have not been characterized., Hypothesis: Anticoagulation strategies and outcomes differ by anticoagulant type in patients undergoing CIED implantation., Methods: Using the nationwide Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we assessed how atrial fibrillation (AF) patients undergoing CIED implantation were cared for and their subsequent outcomes. Outcomes were compared by oral anticoagulant therapy (none, warfarin, or NOAC) as well as by anticoagulation interruption status., Results: Among 9129 AF patients, 416 (5%) underwent CIED implantation during a median follow-up of 30 months (interquartile range, 24-36). Of these, 60 (14%) had implantation on a NOAC. Relative to warfarin therapy, those on a NOAC were younger (70.5 years [range, 65-77.5 years] vs 77 years [range, 70-82 years]), had less valvular heart disease (15.0% vs 31.3%), higher creatinine clearance (67.3 [range, 59.7-99.0] vs 65.8 [range, 50.0-91.6]), were more likely to have persistent AF (26.7% vs 22.9%), and use concomitant aspirin (51.7% vs 35.2%). OAC therapy was commonly interrupted for CIED in 64% (n = 183 of 284) of warfarin patients and 65% (n = 39 of 60) of NOAC patients. Many interrupted patients received intravenous bridging anticoagulation: 33/183 (18%) interrupted warfarin and 4/39 (10%) interrupted NOAC patients. Thirty-day periprocedure bleeding and stroke adverse events were infrequent., Conclusions: Management of anticoagulation among AF patients undergoing CIED implantation is highly variable, with OAC being interrupted in more than half of both warfarin- and NOAC-treated patients. Bleeding and stroke events were infrequent in both warfarin and NOAC-treated patients., (© 2017 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Aims: The presence of cancer can complicate treatment choices for patients with atrial fibrillation (AF) increasing both the risk of thrombotic and bleeding events., Methods and Results: Using data from Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we aimed to characterize AF patients with cancer, to describe their management and to assess the association between cancer and cardiovascular (CV) outcomes. Among 9749 patients, 23.8% had history of cancer (57% solid malignancy, 1.3% leukaemia, 3.3% lymphoma, 40% other type, and 2.2% metastatic cancer). Patients with history of cancer were older, more likely to have CV disease, CV risk factors, and prior gastrointestinal bleeding. No difference in antiarrhythmic and antithrombotic therapy was observed between those with and without cancer. Patients with history of cancer had a significantly higher risk of death (7.8 vs. 4.9 deaths per 100 patient-years follow-up, P = 0.0003) mainly driven by non-CV death (4.2 vs. 2.4 per 100 patient-years follow-up; P = 0.0004) and higher risk of major bleeding (5.1 vs. 3.5 per 100 patient-years follow-up; P = 0.02) compared with non-cancer patients; no differences were observed in risks of strokes/non-central nervous system embolism (1.96 vs. 1.48, P = 0.74) and CV death (2.89 vs. 2.07, P = 0.35) between the two groups., Conclusion: A history of cancer is common among AF patients with up to one in four patients having both. Antithrombotic therapy, rates of cerebrovascular accident, other thrombotic events and cardiac death were similar in AF patients with or without a history of cancer. Patients with cancer, however, were at higher risk of major bleeding and non-CV death., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Objectives: To explore barriers to anticoagulation in older adults with atrial fibrillation (AF) at high risk of stroke and to identify opportunities for interventions that might increase use of oral anticoagulants (OACs)., Design: Retrospective cohort study., Setting: Two large community-based AF cohorts., Participants: Individuals with ischemic stroke surviving hospitalization (N = 1,405, mean age 79)., Measurements: Using structured chart review, reasons for nonuse of OAC were identified, and 1-year poststroke survival was assessed. Logistic regression was used to identify correlates of OAC nonuse., Results: Median CHA 2 DS 2 -VASc score was 5, yet 44% of participants were not prescribed an OAC at discharge. The most-frequent (nonmutually exclusive) physician reasons for not prescribing OAC included fall risk (26.7%), poor prognosis (19.3%), bleeding history (17.1%), participant or family refusal (14.9%), older age (11.0%), and dementia (9.4%). Older age (odds ratio (OR) = 8.96, 95% confidence interval (CI) = 5.01-16.04 for aged ≥85 vs <65) and disability (OR = 12.58, 95% CI = 5.82-27.21 for severe vs no deficit) were the most-important independent predictors of nonuse of OACs. By 1 year, 42.5% of those not receiving an OAC at discharge had died, versus 19.1% of those receiving an OAC (P < .001), far higher than recurrent stroke rates., Conclusion: Despite very high stroke risk, more than 40% of participants were not discharged with an OAC. Dominant reasons included fall risk, poor prognosis, older age, and dementia. These individuals' high 1-year mortality rate confirmed their high level of comorbidity. To improve anticoagulation decisions and outcomes in this population, future research should focus on strategies to mitigate fall risk, improve assessment of risks and benefits of anticoagulation in individuals with AF, and determine whether newer anticoagulants are safer in complex elderly and frail individuals., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

Objectives: To provide greater understanding of the "real world" effect of anticoagulation on stroke risk over several years., Design: Cohort study., Setting: Anticoagulation and Risk Factors in Atrial Fibrillation Study community-based cohort., Participants: Adults with nonvalvular atrial fibrillation (AF) between 1996 and 2003 (13,559)., Measurements: All events were clinician adjudicated. Extended Cox regression with longitudinal warfarin exposure was used to estimate cause-specific hazard ratios (HRs) for thromboembolism and the competing risk event (all cause death). The Fine and Gray subdistribution regression approach was used to estimate this association while accounting for competing death events. As a secondary analysis, follow-up was limited to 1, 3, and 5 years., Results: The rate of death was much higher in the group not taking warfarin (8.1 deaths/100 person-years (PY)) than in the group taking warfarin (5.5 deaths/100 PY). The cause-specific HR indicated a large reduction in thromboembolism with warfarin use (adjusted HR = 0.57, 95% confidence interval (CI) = 0.50-0.65), although this association was substantially attenuated after accounting for competing death events (adjusted HR = 0.87, 95% CI = 0.77-0.99). In analyses limited to 1 year of follow-up, with fewer competing death events, the results for models that did and did not account for competing risks were similar., Conclusion: Analyses accounting for competing death events may provide a more-realistic estimate of the longer-term stroke prevention benefits of anticoagulants than traditional noncompeting risk analyses for individuals with AF, particularly those who are not currently treated with anticoagulants., Competing Interests: Dr. Singer serves as a consultant/advisory board member for Bayer Healthcare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Johnson and Johnson, Pfizer, and St. Jude Medical on matters related to preventing stroke in atrial fibrillation and with CSL Behring related to reversal of warfarin anticoagulation. Additionally, Dr. Singer has research contracts with Medtronic, Inc related to atrial fibrillation and risk of stroke, with Johnson and Johnson related to stroke prevention in atrial fibrillation, and with Bristol-Myers Squibb related to atrial fibrillation and risk of stroke. Dr. Go has received research grants from CSL Behring and iRhythm Technologies., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

The decision to use anticoagulants for atrial fibrillation depends on comparing a patient's estimated risk of stroke to their bleeding risk. Several of the risk factors in the stroke risk schemes overlap with hemorrhage risk. We compared how well 2 stroke risk scores (CHADS2 and CHA2DS2-VASc) and 2 hemorrhage risk scores (the ATRIA bleeding score and the HAS-BLED score) predicted major hemorrhage on and off warfarin in a cohort of 13,559 community-dwelling adults with AF. Over a cumulative 64,741 person-years of follow-up, we identified a total of 777 incident major hemorrhage events. The ATRIA bleeding score had the highest predictive ability of all the scores in patients on warfarin (c-index of 0.74 [0.72 to 0.76] compared with 0.65 [0.62 to 0.67] for CHADS2, 0.65 [0.62 to 0.67] for CHA2DS2-VASc, and 0.64 [0.61 to 0.66] for HAS-BLED) and in those off warfarin (0.77 [0.74 to 0.79] compared with 0.67 [0.64 to 0.71] for CHADS2, 0.67 [0.64 to 0.70] for CHA2DS2-VASc, and 0.68 [0.65 to 0.71] for HAS-BLED). In conclusion, although CHADS2 and CHA2DS2-VASc stroke scores were better at predicting hemorrhage than chance alone, they were inferior to the ATRIA bleeding score. Our study supports the use of dedicated hemorrhage risk stratification tools to predict major hemorrhage in atrial fibrillation., Competing Interests: Dr. Singer has served as a Consultant/Advisory Board for: Boehringer Ingelheim, Bristol-Myers Squibb, Johnson and Johnson, Merck, and Pfizer. He received research support from Boehringer Ingelheim, Bristol-Myers Squibb. Dr. Go has received research support from iRhythm and CSL Behring., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The role of triple antithrombotic therapy vs dual antithrombotic therapy in patients with both atrial fibrillation and coronary artery disease remains unclear. This study explores the differences in treatment practices and outcomes between triple antithrombotic therapy and dual antithrombotic therapy in patients with atrial fibrillation and coronary artery disease., Methods: Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (n = 10,135), we analyzed outcomes in patients with coronary artery disease (n = 1827) according to treatment with triple antithrombotic therapy (defined as concurrent therapy with an oral anticoagulant, a thienopyridine, and aspirin) or dual antithrombotic therapy (comprising either an oral anticoagulant and one antiplatelet agent [OAC plus AA] or 2 antiplatelet drugs and no anticoagulant [DAP])., Results: The use of triple antithrombotic therapy, OAC plus AA, and DAP at baseline was 8.5% (n = 155), 80.4% (n = 1468), and 11.2% (n = 204), respectively. Among patients treated with OAC plus AA, aspirin was the most common antiplatelet agent used (90%), followed by clopidogrel (10%) and prasugrel (0.1%). The use of triple antithrombotic therapy was not affected by patient risk of either stroke or bleeding. Patients treated with triple antithrombotic therapy at baseline were hospitalized for all causes (including cardiovascular) more often than patients on OAC plus AA (adjusted hazard ratio 1.75; 95% confidence interval, 1.35-2.26; P <.0001) or DAP (hazard ratio 1.82; 95% confidence interval, 1.25-2.65; P = .0018). Rates of major bleeding or a combined cardiovascular outcome were not significantly different by treatment group., Conclusions: Choice of antithrombotic therapy in patients with atrial fibrillation and coronary artery disease was not affected by patient stroke or bleeding risks. Triple antithrombotic therapy-treated patients were more likely to be hospitalized for all causes than those on OAC plus AA or on DAP., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To characterize warfarin eligibility and receipt among Veterans Health Administration (VHA) patients with and without mental health conditions (MHCs)., Study Design: Retrospective cohort study., Methods: This observational study identified VHA atrial fibrillation (AF) patients with and without MHCs in 2004. We examined unadjusted MHC-related differences in warfarin eligibility and warfarin receipt among warfarin-eligible patients, using logistic regression for any MHC and for specific MHCs (adjusting for sociodemographic and clinical characteristics)., Results: Of 125,670 patients with AF, most (96.8%) were warfarin-eligible based on a CHADS2 stroke risk score. High stroke risk and contraindications to anticoagulation were both more common in patients with MHC. Warfarin-eligible patients with MHC were less likely to receive warfarin than those without MHC (adjusted odds ratio [AOR], 0.90; 95% CI, 0.87-0.94). The association between MHC and warfarin receipt among warfarin-eligible patients varied by specific MHC. Patients with anxiety disorders (AOR, 0.86; 95% CI, 0.80-0.93), psychotic disorders (AOR, 0.77; 95% CI, 0.65-0.90), and alcohol use disorders (AOR 0.62, 95% CI 0.54-0.72) were less likely to receive warfarin than patients without these conditions, whereas patients with depressive disorders and posttraumatic stress disorder were no less likely to receive warfarin than patients without these conditions., Conclusions: Compared with patients with AF without MHCs, those with MHCs are less likely to be eligible for warfarin receipt and, among those eligible, are less likely to receive such treatment. Although patients with AF with MHC need careful assessment of bleeding risk, this finding suggests potential missed opportunities for more intensive therapy among some individuals with MHCs.

Background: Time in therapeutic range (TTR) of international normalized ratio (INR) of 2.0 to 3.0 is important for the safety and effectiveness of warfarin anticoagulation. There are few data on TTR among patients with atrial fibrillation (AF) in community-based clinical practice., Methods: Using the US Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), we examined TTR (using a modified Rosendaal method) among 5,210 patients with AF on warfarin and treated at 155 sites. Patients were grouped into quartiles based on TTR data. Multivariable logistic regression modeling with generalized estimating equations was used to determine patient and provider factors associated with the lowest (worst) TTR., Results: Overall, 59% of the measured INR values were between 2.0 and 3.0, with an overall mean and median TTR of 65% ± 20% and 68% (interquartile range [IQR] 53%-79%). The median times below and above the therapeutic range were 17% (IQR 8%-29%) and 10% (IQR 3%-19%), respectively. Patients with renal dysfunction, advanced heart failure, frailty, prior valve surgery, and higher risk for bleeding (ATRIA score) or stroke (CHA2DS2-VASc score) had significantly lower TTR (P < .0001 for all). Patients treated at anticoagulation clinics had only slightly higher median TTR (69%) than those not (66%) (P < .0001)., Conclusions: Among patients with AF in US clinical practices, TTR on warfarin is suboptimal, and those at highest predicted risks for stroke and bleeding were least likely to be in therapeutic range., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Recent clinical trials have demonstrated the safety and efficacy of several non-vitamin K oral anticoagulants (NOACs) for the treatment of atrial fibrillation (AF). However, there are limited data on their use and outcomes in routine clinical practice, particularly among patients newly diagnosed as having AF and patients with AF recently transitioned to a NOAC., Methods/design: ORBIT-AF II is a multicenter, national registry of patients with AF that is enrolling up to 15,000 newly diagnosed patients with AF and/or those with AF recently transitioned to a NOAC from 300 US outpatient practices. These patients will be followed for up to 2 years, including clinical status, outcomes (major adverse cardiovascular events, bleeding), and management of anticoagulation surrounding bleeding events. In addition, detailed data regarding the use of these agents in and around cardiac procedures, their complications, and management of such complications will be collected., Conclusions: The ORBIT-AF II registry will provide valuable insights into the safety and effectiveness of NOACs used in AF in community practice settings., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background: The role of concomitant aspirin (ASA) therapy in patients with atrial fibrillation (AF) receiving oral anticoagulation (OAC) is unclear. We assessed concomitant ASA use and its association with clinical outcomes among AF patients treated with OAC., Methods and Results: The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry enrolled 10 126 AF patients from 176 US practices from June 2010 through August 2011. The study population was limited to those on OAC (n=7347). Hierarchical multivariable logistic regression models were used to assess factors associated with concomitant ASA therapy. Primary outcomes were 6-month bleeding, hospitalization, ischemic events, and mortality. Overall, 35% of AF patients (n=2543) on OAC also received ASA (OAC+ASA). Patients receiving OAC+ASA were more likely to be male (66% versus 53%; P<0.0001) and had more comorbid illness than those on OAC alone. More than one third of patients (39%) receiving OAC+ASA did not have a history of atherosclerotic disease, yet 17% had elevated Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) bleeding risk scores (≥5). Major bleeding (adjusted hazard ratio, 1.53; 95% confidence interval, 1.20-1.96) and bleeding hospitalizations (adjusted hazard ratio, 1.52; 95% confidence interval, 1.17-1.97) were significantly higher in those on OAC+ASA compared with those on OAC alone. Rates of ischemic events were low., Conclusions: Patients with AF receiving OAC are often treated with concomitant ASA, even when they do not have cardiovascular disease. Use of OAC+ASA was associated with significantly increased risk for bleeding, emphasizing the need to carefully determine if and when the benefits of concomitant ASA outweigh the risks in AF patients already on OAC., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT01165710.

Background: Patients with atrial fibrillation (AF) at the highest stroke risk derive the largest benefit from oral anticoagulation (OAC). Those with the highest stroke risk have been paradoxically less likely to receive OAC. This study assessed the association between stroke and bleeding risk on rates of OAC., Methods and Results: We analyzed OAC use among 10,098 patients with AF from 174 community-based outpatient practices enrolled in 2010-2011 in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). OAC was defined as warfarin or dabigatran use at study enrollment. Stroke and bleeding risk were calculated using congestive heart failure, hypertension, age, diabetes mellitus, prior stroke (CHADS₂), and anticoagulation and risk factors in AF (ATRIA) scores, respectively. The mean subject age was 73 years; 58% were men. Overall, 76% of patients received OAC (71% warfarin and 5% dabigatran). The use of OAC increased among those with higher CHADS₂ scores, from 53% for CHADS₂=0 to 80% for CHADS₂≥2 (P<0.001). OAC use fell slightly with increasing ATRIA bleeding risk score, from 81% for ATRIA=3 to 73% for ATRIA≥5 (P<0.001). A significant interaction existed between ATRIA and CHADS₂ scores (P=0.021). Among those with low bleeding risk, use of OAC increased significantly with increasing stroke risk. Among those with high bleeding risk, CHADS₂ stroke risk had a smaller impact on use of OAC., Conclusions: In community-based outpatients with AF, use of OAC was high and driven by not only predominantly stroke but also bleeding risk. Stroke risk significantly affects OAC use among those with low bleeding risk, whereas those with high bleeding risk demonstrate consistently lower use of OAC regardless of stroke risk.

Background and Purpose: Prescribing warfarin for atrial fibrillation depends in large part on the expected reduction in ischemic stroke risk versus the expected increased risk of intracranial hemorrhage (ICH). However, the anticoagulation decision also depends on the relative severity of such events. We assessed the impact of anticoagulation on 30-day mortality from ischemic stroke versus ICH in a large community-based cohort of patients with atrial fibrillation., Methods: We followed 13,559 patients with atrial fibrillation enrolled in an integrated healthcare delivery system for a median 6 years. Incident ischemic strokes and ICHs were identified from computerized databases and validated through medical record review. The association of warfarin and international normalized ratio at presentation with 30-day mortality was modeled using multivariable logistic regression adjusting for clinical factors., Results: We identified 1025 incident ischemic strokes and 299 ICHs during follow-up. Compared with no antithrombotic therapy, warfarin was associated with reduced Rankin score and lower 30-day mortality from ischemic stroke (adjusted OR, 0.64; 95% CI, 0.45-0.91) but a higher mortality from ICH (OR, 1.62; 95% CI, 0.88-2.98). Therapeutic international normalized ratios (2-3) were associated with an especially low ischemic stroke mortality (OR, 0.38; 95% CI, 0.20-0.70), whereas international normalized ratios>3 increased the odds of dying of ICH by 2.66-fold (95% CI, 1.21-5.86)., Conclusions: Warfarin reduces 30-day mortality from ischemic stroke but increases ICH-related mortality. Both effects on event severity as well as on event rates need to be incorporated into rational decision-making about anticoagulants for atrial fibrillation.

Background: The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios., Methods: We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement., Results: For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS(2) [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS(2) score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS(2) score of ≥ 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy., Conclusions: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS(2) score of ≥ 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized approach.

Objectives: To determine whether atrial fibrillation (AF) patients with mental health conditions (MHCs) were less likely than AF patients without MHCs to be prescribed warfarin and, if receiving warfarin, to maintain an International Normalized Ratio (INR) within the therapeutic range., Study Design: Detailed chart review of AF patients using a Veterans Health Administration (VHA) facility in 2003., Methods: For a random sample of 296 AF patients, records identified clinician-diagnosed MHCs (independent variable) and AF-related care in 2003 (dependent variables), receipt of warfarin, INR values below/above key thresholds, and time spent within the therapeutic range (2.0-3.0) or highly out of range. Differences between the MHC and comparison groups were examined using X2 tests and logistic regression controlling for age and comorbidity., Results: Among warfarin-eligible AF patients (n = 246), 48.5% of those with MHCs versus 28.9% of those without MHCs were not treated with warfarin (P = .004). Among those receiving warfarin and monitored in VHA, highly supratherapeutic INRs were more common in the MHC group; for example, 27.3% versus 1.6% had any INR >5.0 (P <.001). Differences persisted after adjusting for age and comorbidity., Conclusions: MHC patients with AF were less likely than those without MHC to have adequate management of their AF care. Interventions directed at AF patients with MHC may help to optimize their outcomes.

Objectives: The purpose of this study was to develop a risk stratification score to predict warfarin-associated hemorrhage., Background: Optimal decision making regarding warfarin use for atrial fibrillation requires estimation of hemorrhage risk., Methods: We followed up 9,186 patients with atrial fibrillation contributing 32,888 person-years of follow-up on warfarin, obtaining data from clinical databases and validating hemorrhage events using medical record review. We used Cox regression models to develop a hemorrhage risk stratification score, selecting candidate variables using bootstrapping approaches. The final model was internally validated by split-sample testing and compared with 6 published hemorrhage risk schemes., Results: We observed 461 first major hemorrhages during follow-up (1.4% annually). Five independent variables were included in the final model and weighted by regression coefficients: anemia (3 points), severe renal disease (e.g., glomerular filtration rate <30 ml/min or dialysis-dependent, 3 points), age ≥75 years (2 points), prior bleeding (1 point), and hypertension (1 point). Major hemorrhage rates ranged from 0.4% (0 points) to 17.3% per year (10 points). Collapsed into a 3-category risk score, major hemorrhage rates were 0.8% for low risk (0 to 3 points), 2.6% for intermediate risk (4 points), and 5.8% for high risk (5 to 10 points). The c-index for the continuous risk score was 0.74 and 0.69 for the 3-category score, higher than in the other risk schemes. There was net reclassification improvement versus all 6 comparators (from 27% to 56%)., Conclusions: A simple 5-variable risk score was effective in quantifying the risk of warfarin-associated hemorrhage in a large community-based cohort of patients with atrial fibrillation., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Warfarin reduces the risk for ischemic stroke in patients with atrial fibrillation (AF) but increases the risk for hemorrhage. Dabigatran is a fixed-dose, oral direct thrombin inhibitor with similar or reduced rates of ischemic stroke and intracranial hemorrhage in patients with AF compared with those of warfarin., Objective: To estimate the quality-adjusted survival, costs, and cost-effectiveness of dabigatran compared with adjusted-dose warfarin for preventing ischemic stroke in patients 65 years or older with nonvalvular AF., Design: Markov decision model., Data Sources: The RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial and other published studies of anticoagulation. The cost of dabigatran was estimated on the basis of pricing in the United Kingdom., Target Population: Patients aged 65 years or older with nonvalvular AF and risk factors for stroke (CHADS₂ score ≥1 or equivalent) and no contraindications to anticoagulation., Time Horizon: Lifetime., Perspective: Societal., Intervention: Warfarin anticoagulation (target international normalized ratio, 2.0 to 3.0); dabigatran, 110 mg twice daily (low dose); and dabigatran, 150 mg twice daily (high dose)., Outcome Measures: Quality-adjusted life-years (QALYs), costs (in 2008 U.S. dollars), and incremental cost-effectiveness ratios., Results of Base-Case Analysis: The quality-adjusted life expectancy was 10.28 QALYs with warfarin, 10.70 QALYs with low-dose dabigatran, and 10.84 QALYs with high-dose dabigatran. Total costs were $143 193 for warfarin, $164 576 for low-dose dabigatran, and $168 398 for high-dose dabigatran. The incremental cost-effectiveness ratios compared with warfarin were $51 229 per QALY for low-dose dabigatran and $45 372 per QALY for high-dose dabigatran., Results of Sensitivity Analysis: The model was sensitive to the cost of dabigatran but was relatively insensitive to other model inputs. The incremental cost-effectiveness ratio increased to $50 000 per QALY at a cost of $13.70 per day for high-dose dabigatran but remained less than $85 000 per QALY over the full range of model inputs evaluated. The cost-effectiveness of high-dose dabigatran improved with increasing risk for stroke and intracranial hemorrhage., Limitation: Event rates were largely derived from a single randomized clinical trial and extrapolated to a 35-year time frame from clinical trials with approximately 2-year follow-up., Conclusion: In patients aged 65 years or older with nonvalvular AF at increased risk for stroke (CHADS₂ score ≥1 or equivalent), dabigatran may be a cost-effective alternative to warfarin depending on pricing in the United States., Primary Funding Source: American Heart Association and Veterans Affairs Health Services Research & Development Service.

Background: Guidelines recommend warfarin use in patients with atrial fibrillation solely on the basis of risk for ischemic stroke without antithrombotic therapy. These guidelines rely on ischemic stroke rates observed in older trials and do not explicitly account for increased risk for hemorrhage., Objective: To quantify the net clinical benefit of warfarin therapy in a cohort of patients with atrial fibrillation., Design: Mixed retrospective and prospective cohort study of patients with atrial fibrillation between 1996 and 2003., Setting: An integrated health care delivery system., Patients: 13 559 adults with nonvalvular atrial fibrillation., Measurements: Warfarin exposure, patient characteristics, CHADS(2) score (1 point for each of congestive heart failure, hypertension, age, and diabetes and 2 points for stroke), and outcome events were ascertained from health plan records and databases. Net clinical benefit was defined as the annual rate of ischemic strokes and systemic emboli prevented by warfarin minus intracranial hemorrhages attributable to warfarin, multiplied by an impact weight. The base-case impact weight was 1.5, reflecting the greater clinical impact of intracranial hemorrhage versus thromboembolism., Results: Patients accumulated more than 66 000 person-years of follow-up. The adjusted net clinical benefit of warfarin for the cohort overall was 0.68% per year (95% CI, 0.34% to 0.87%). Adjusted net clinical benefit was greatest for patients with a history of ischemic stroke (2.48% per year [CI, 0.75% to 4.22%]) and for those 85 years or older (2.34% per year [CI, 1.29% to 3.30%]). The net clinical benefit of warfarin increased from essentially zero in CHADS(2) stroke risk categories 0 and 1 to 2.22% per year (CI, 0.58% to 3.75%) in CHADS(2) categories 4 to 6. The patterns of results were preserved when weighting factors for intracranial hemorrhage of 1.0 and 2.0 were used., Limitations: Residual confounding is a possibility. Some outcome events were probably missed by the screening algorithm or when medical records were unavailable., Conclusion: Expected net clinical benefit of warfarin therapy is highest among patients with the highest untreated risk for stroke, which includes the oldest age category. Risk assessment that incorporates both risk for thromboembolism and risk for intracranial hemorrhage provides a more quantitatively informed basis for the decision on antithrombotic therapy in patients with atrial fibrillation., Primary Funding Source: National Institute on Aging; National Heart, Lung, and Blood Institute; and Massachusetts General Hospital.

Background: Randomized trials and observational studies support using an international normalized ratio (INR) target of 2.0 to 3.0 for preventing ischemic stroke in atrial fibrillation. We assessed whether the INR target should be adjusted based on selected patient characteristics., Methods and Results: We conducted a case-control study nested within the ATRIA cohort's 9217 atrial fibrillation patients taking warfarin to define the relationship between INR level and the odds of thromboembolism (TE; mainly stroke) and of intracranial hemorrhage (ICH) relative to INR 2.0 to 2.5. We identified 396 TE cases and 164 ICH cases during follow-up. Each case was compared with 4 randomly selected controls matched on calendar date and stroke risk factors using matched univariable analyses and conditional logistic regression. We explored modification of the INR-outcome relationships by the following stroke risk factors: prior stroke, age, and CHADS(2) risk score. Overall, the odds of TE were low and stable above INR 1.8. Compared with INR 2.0 to 2.5, the relative odds of TE increased strikingly at INR <1.8 (eg, odds ratio, 3.72; 95% CI, 2.67 to 5.19, at INR 1.4 to 1.7). The odds of ICH increased markedly at INR values >3.5 (eg, odds ratio, 3.56; 95% CI: 1.70 to 7.46, at INR 3.6 to 4.5). The relative odds of ICH were consistently low at INR <3.6. There was no evidence of lower ICH risk at INR levels <2.0. These patterns of risk did not differ substantially by history of stroke, age, or CHADS(2) risk score., Conclusions: Our results confirm that the current standard of INR 2.0 to 3.0 for atrial fibrillation falls in the optimal INR range. Our findings do not support adjustment of INR targets according to previously defined stroke risk factors.

Atrial fibrillation (AF) is the most common sustained arrhythmia seen in clinical practice. It affects approximately 6% of persons over 65 years of age and is independently associated with a 4- to 5-fold higher risk of ischaemic stroke and a 2-fold higher risk of death. Randomized controlled trials have shown that treatment with adjusted-dose oral vitamin K antagonists (primarily warfarin with a target international normalized ratio [INR] of 2.0-3.0) reduces the relative risk of ischaemic stroke by two-thirds (an approximately 3% reduction in annual absolute risk), but is associated with a 0.2% excess annual absolute risk of intracranial haemorrhage (ICH). However, in 'real world' studies, the risk reductions in ischaemic stroke with warfarin have been significantly lower (25-50% relative risk reduction) than in selected trial samples. Moreover, more than 90% of patients enrolled in the sentinel trials were White/European. This raises the question of whether the beneficial results of warfarin can be extrapolated to persons of colour. Important differences in stroke risk profile and responsiveness to warfarin exist across racial/ethnic groups, such that one cannot assume a priori that there is a net benefit of warfarin therapy for AF patients of all racial/ethnic groups.Among patients with ischaemic stroke, AF is more likely to be implicated as the cause of stroke in the White population than in other racial/ethnic groups. Furthermore, AF may be a stronger predictor of ischaemic stroke among the White population than in Black or Hispanic/Latino populations. Approximately one-third of strokes in AF patients are noncardioembolic. Warfarin has been shown to be ineffective in preventing recurrent noncardioembolic strokes. Many persons of colour with AF have other risk factors that predispose them to noncardioembolic stroke, which may partially explain why warfarin has been reported to be less efficacious in preventing strokes in non-White patients with AF, even after adjustment for co-morbidities and anticoagulation monitoring. Notably, the background incidence of ICH is higher in Black, Hispanic and Asian patients than in White patients. Any greater than expected increases in bleeding secondary to anticoagulation may potentially offset any benefit gained from cardioembolic stroke reduction, although this has not been fully resolved.Finally, there are racial/ethnic differences in the prevalence of certain polymorphisms in genes that influence warfarin pharmacokinetics and pharmacodynamics (e.g. cytochrome P450 2C9 and vitamin K epoxide reductase). The Asian population generally appear to require the lowest daily dose of warfarin to maintain a given INR target, with the White population requiring an intermediate daily dose and the Black population requiring the highest daily dose. These differences must be taken into account when administering warfarin in order to minimize the risk of under- or over-anticoagulation.In summary, warfarin is highly effective in preventing ischaemic strokes in White patients with AF at a modestly higher risk of ICH. Whether the same net clinical benefit extends to persons of colour is unproven. Given the rapidly changing demographic nationally and internationally, additional research is needed to resolve this important question.

Objectives: Little is known about the outcomes of patients who have hemorrhagic complications while receiving warfarin therapy. We examined the rates of death and disability resulting from warfarin-associated intracranial and extracranial hemorrhages in a large cohort of patients with atrial fibrillation., Methods: We assembled a cohort of 13,559 adults with nonvalvular atrial fibrillation and identified patients hospitalized for warfarin-associated intracranial and major extracranial hemorrhage. Data on functional disability at discharge and 30-day mortality were obtained from a review of medical charts and state death certificates. The relative odds of 30-day mortality by hemorrhage type were calculated using multivariable logistic regression., Results: We identified 72 intracranial and 98 major extracranial hemorrhages occurring in more than 15,300 person-years of warfarin exposure. At hospital discharge, 76% of patients with intracranial hemorrhage had severe disability or died, compared with only 3% of those with major extracranial hemorrhage. Of the 40 deaths from warfarin-associated hemorrhage that occurred within 30 days, 35 (88%) were from intracranial hemorrhage. Compared with extracranial hemorrhages, intracranial events were strongly associated with 30-day mortality (odds ratio 20.8 [95% confidence interval, 6.0-72]) even after adjusting for age, sex, anticoagulation intensity on admission, and other coexisting illnesses., Conclusions: Among anticoagulated patients with atrial fibrillation, intracranial hemorrhages caused approximately 90% of the deaths from warfarin-associated hemorrhage and the majority of disability among survivors. When considering anticoagulation, patients and clinicians need to weigh the risk of intracranial hemorrhage far more than the risk of all major hemorrhages.

Objectives: To assess whether older age is independently associated with hemorrhage risk in patients with atrial fibrillation, whether or not they are taking warfarin therapy., Design: Cohort study., Setting: Integrated healthcare delivery system. Thirteen thousand five hundred fifty-nine adults with nonvalvular atrial fibrillation., Measurements: Patient data were collected from automated clinical and administrative databases using previously validated search algorithms. Medical charts were reviewed from patients hospitalized were for major hemorrhage (intracranial, fatal, requiring >or=2 units of transfused blood, or involving a critical anatomic site). Age was categorized into four categories (<60, 60-69, 70-79, and >or=80), and multivariable Poisson regression was used to assess whether major hemorrhage rates increased with age, stratified by warfarin use and adjusted for other clinical risk factors for hemorrhage., Results: A total of 170 major hemorrhages were identified during 15,300 person-years of warfarin therapy and 162 major hemorrhages during 15,530 person-years off warfarin therapy. Hemorrhage rates rose with older age, with an average increase in hemorrhage rate of 1.2 (95% confidence interval (CI) 1.0-1.4) per older age category in patients taking warfarin and 1.5 (95% CI=1.3-1.8) in those not taking warfarin. Intracranial hemorrhage rates were significantly higher in those aged 80 and older (adjusted rate ratio=1.8, 95% CI=1.1-3.1 for those taking warfarin, adjusted rate ratio=4.7, 95% CI=2.4-9.2 for those not taking warfarin) than in those younger than 80., Conclusion: Older age increases the risk of major hemorrhage, particularly intracranial hemorrhage, in patients with atrial fibrillation, whether or not they are taking warfarin. Hemorrhage rates were generally comparable with those reported in previous randomized trials, indicating that carefully monitored warfarin therapy can be used with reasonable safety in older patients.

Background: The risk for atrial fibrillation-associated stroke increases at low anticoagulation intensities. However, higher intensities increase hemorrhage risk. Optimal use of warfarin for atrial fibrillation requires precise information on the risk for intracranial hemorrhage as a function of patient age and anticoagulation intensity., Objective: To examine the relationship of age, anticoagulation intensity, and risk for intracranial hemorrhage., Design: Case-control study., Setting: Academic medical center., Patients: 170 case-patients who developed intracranial hemorrhage during warfarin therapy and 1020 matched controls who did not; both case-patients and controls were taking warfarin for atrial fibrillation., Measurements: The authors performed multivariable conditional logistic regression to determine the odds of intracranial hemorrhage with regard to age and international normalized ratio (INR), controlling for comorbid conditions and aspirin use., Results: Case-patients were older than controls (median age, 78 years vs. 75 years; P < 0.001) and had higher median INRs (2.7 vs. 2.3; P < 0.001). The risk for intracranial hemorrhage increased at 85 years of age or older (adjusted odds ratio, 2.5 [95% CI, 1.3 to 4.7]; referent age, 70 to 74 years) and at an INR range of 3.5 to 3.9 (adjusted odds ratio, 4.6 [CI, 2.3 to 9.4]; referent INR, 2.0 to 3.0). The risk for intracranial hemorrhage at INRs less than 2.0 did not differ statistically from the risk at INRs of 2.0 to 3.0 (adjusted odds ratio, 1.3 [CI, 0.8 to 2.2])., Limitations: Although duration of anticoagulation has been associated with hemorrhage in other studies, the current study could not control for this potential confounder., Conclusions: The risk for intracranial hemorrhage increases at age 85 years. International normalized ratios less than 2.0 were not associated with lower risk for intracranial hemorrhage compared with INRs between 2.0 and 3.0. Therefore, anticoagulation management should focus on maintaining INRs in the 2.0 to 3.0 range, even in elderly patients with atrial fibrillation, rather than targeting INRs less than 2.0. Similarly, INRs of 3.5 or greater should be avoided.

As one of the most powerful independent risk factors for ischemic stroke and the most clinically relevant arrhythmia, atrial fibrillation (AF) poses a serious clinical and public health threat as the global population ages. AF increases the risk of ischemic stroke 4- to 5-fold although this statistic varies with age of the patient. Indeed, the prevalence rises to 1 in 25 people aged > or =60 years and 1 in 10 people aged > or =80 years. More than 2.3 million Americans have diagnosed AF, and that number is expected to increase dramatically over the coming decades. Ischemic stroke causes the most major disability and remains the third leading cause of death in the United States. Therapeutic strategies and optimal risk stratification offer the best hope for decreasing the burden of AF-related thromboembolism. This article focuses on the randomized trial evidence for the efficacy and safety of oral vitamin K antagonists (eg, warfarin) for stroke prevention in AF. In particular, this article explores how well these findings translate into clinical practice, especially among patients with AF treated outside of clinical trials. Discussion centers on using evidence-based data to guide treatment for patients who are at increased risk for stroke. Such strategies would enhance the net benefit of oral anticoagulation. Concluding points provide information on improving risk stratification for stroke in patients with AF.

Context: Warfarin has been shown to be highly efficacious for preventing thromboembolism in atrial fibrillation in randomized trials, but its effectiveness and safety in clinical practice is less clear., Objective: To evaluate the effect of warfarin on risk of thromboembolism, hemorrhage, and death in atrial fibrillation within a usual care setting., Design: Cohort study assembled between July 1, 1996, and December 31, 1997, and followed up through August 31, 1999., Setting: Large integrated health care system in Northern California., Patients: Of 13,559 adults with nonvalvular atrial fibrillation, 11,526 were studied, 43% of whom were women, mean age 71 years, with no known contraindications to anticoagulation at baseline., Main Outcomes: Ischemic stroke, peripheral embolism, hemorrhage, and death according to warfarin use and comorbidity status, as determined by automated databases, review of medical records, and state mortality files., Results: Among 11,526 patients, 397 incident thromboembolic events (372 ischemic strokes, 25 peripheral embolism) occurred during 25,341 person-years of follow-up, and warfarin therapy was associated with a 51% (95% confidence interval [CI], 39%-60%) lower risk of thromboembolism compared with no warfarin therapy (either no antithrombotic therapy or aspirin) after adjusting for potential confounders and likelihood of receiving warfarin. Warfarin was effective in reducing thromboembolic risk in the presence or absence of risk factors for stroke. A nested case-control analysis estimated a 64% reduction in odds of thromboembolism with warfarin compared with no antithrombotic therapy. Warfarin was also associated with a reduced risk of all-cause mortality (adjusted hazard ratio, 0.69; 95% CI, 0.61-0.77). Intracranial hemorrhage was uncommon, but the rate was moderately higher among those taking vs those not taking warfarin (0.46 vs 0.23 per 100 person-years, respectively; P =.003, adjusted hazard ratio, 1.97; 95% CI, 1.24-3.13). However, warfarin therapy was not associated with an increased adjusted risk of nonintracranial major hemorrhage. The effects of warfarin were similar when patients with contraindications at baseline were analyzed separately or combined with those without contraindications (total cohort of 13,559)., Conclusions: Warfarin is very effective for preventing ischemic stroke in patients with atrial fibrillation in clinical practice while the absolute increase in the risk of intracranial hemorrhage is small. Results of randomized trials of anticoagulation translate well into clinical care for patients with atrial fibrillation.

Background: The incidence of stroke in patients with atrial fibrillation is greatly reduced by oral anticoagulation, with the full effect seen at international normalized ratio (INR) values of 2.0 or greater. The effect of the intensity of oral anticoagulation on the severity of atrial fibrillation-related stroke is not known but is central to the choice of the target INR., Methods: We studied incident ischemic strokes in a cohort of 13,559 patients with nonvalvular atrial fibrillation. Strokes were identified through hospitalization data bases and validated on the basis of medical records, which also provided information on the use of warfarin or aspirin, the INR at admission, and coexisting illnesses. The severity of stroke was graded according to a modified Rankin scale. Thirty-day mortality was ascertained from hospitalization and mortality files., Results: Of 596 ischemic strokes, 32 percent occurred during warfarin therapy, 27 percent during aspirin therapy, and 42 percent during neither type of therapy. Among patients who were taking warfarin, an INR of less than 2.0 at admission, as compared with an INR of 2.0 or greater, independently increased the odds of a severe stroke in a proportional-odds logistic-regression model (odds ratio, 1.9; 95 percent confidence interval, 1.1 to 3.4) across three severity categories and the risk of death within 30 days (hazard ratio, 3.4; 95 percent confidence interval, 1.1 to 10.1). An INR of 1.5 to 1.9 at admission was associated with a mortality rate similar to that for an INR of less than 1.5 (18 percent and 15 percent, respectively). The 30-day mortality rate among patients who were taking aspirin at the time of the stroke was similar to that among patients who were taking warfarin and who had an INR of less than 2.0., Conclusions: Among patients with nonvalvular atrial fibrillation, anticoagulation that results in an INR of 2.0 or greater reduces not only the frequency of ischemic stroke but also its severity and the risk of death from stroke. Our findings provide further evidence against the use of lower INR target levels in patients with atrial fibrillation., (Copyright 2003 Massachusetts Medical Society)

BackgroundManagement of adults with atrial fibrillation (AF) or atrial flutter in the emergency department (ED) includes rate reduction, cardioversion, and stroke prevention. Different approaches to these components of care may lead to variation in frequency of hospitalization and stroke prevention actions, with significant implications for patient experience, cost of care, and risk of complications. Standardization using evidence-based recommendations could reduce variation in management, preventable hospitalizations, and stroke risk.MethodsWe describe the rationale for our ED-based AF treatment recommendations. We also describe the development of an electronic clinical decision support system (CDSS) to deliver these recommendations to emergency physicians at the point of care. We implemented the CDSS at three pilot sites to assess feasibility and solicit user feedback. We will evaluate the impact of the CDSS on hospitalization and stroke prevention actions using a stepped-wedge cluster randomized pragmatic clinical trial across 13 community EDs in Northern California.DiscussionWe hypothesize that the CDSS intervention will reduce hospitalization of adults with isolated AF or atrial flutter presenting to the ED and increase anticoagulation prescription in eligible patients at the time of ED discharge and within 30 days. If our hypotheses are confirmed, the treatment protocol and CDSS could be recommended to other EDs to improve management of adults with AF or atrial flutter.Trial registrationClinicalTrials.gov NCT05009225 .  Registered on 17 August 2021.

Treatment options for patients with venous thromboembolism (VTE) include warfarin and direct oral anticoagulants (DOACs). Although DOACs are easier to administer than warfarin and do not require routine laboratory monitoring, few studies have directly assessed whether patients are more satisfied with DOACs. We surveyed adults from two large integrated health systems taking DOACs or warfarin for incident VTE occurring between January 1, 2015 and June 30, 2018. Treatment satisfaction was assessed using the validated Anti-Clot Treatment Scale (ACTS), divided into the ACTS Burdens and ACTS Benefits scores; higher scores indicate greater satisfaction. Mean treatment satisfaction was compared using multivariable linear regression, adjusting for patient demographic and clinical characteristics. The effect size of the difference in means was calculated using a Cohen's d (0.20 is considered a small effect and ≥ 0.80 is considered large). We surveyed 2217 patients, 969 taking DOACs and 1248 taking warfarin at the time of survey. Thirty-one point five percent of the cohort was aged ≥ 75 years and 43.1% were women. DOAC users were on average more satisfied with anticoagulant treatment, with higher adjusted mean ACTS Burdens (50.18 v. 48.01, p

Anticoagulation is highly effective for the prevention of stroke in patients with atrial fibrillation (AF) but it is dependent on patients continuing therapy. While studies have demonstrated suboptimal therapeutic persistence on warfarin, few have studied persistence rates with non vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran. We examined rates of continued use of dabigatran versus warfarin over 1 year among AF patients in the ORBIT-AF registry between June 29, 2010 and August 09, 2011. Multivariable logistic regression analysis was used to identify characteristics associated with 1-year persistent use of dabigatran therapy or warfarin. At baseline, 6.4 and 93.6% of 7150 AF patients were on dabigatran and warfarin, respectively. At 12 months, dabigatran-treated patients were less likely to have continued their therapy than warfarin-treated patients [Adjusted persistence rates: 66% (95% CI 60-72) vs. 82% (95% CI 80-84), p

Background Chronic kidney disease ( CKD ) is a common comorbidity in patients with atrial fibrillation. The presence of CKD complicates drug selection for stroke prevention and rhythm control. Methods and Results Patients enrolled in ORBIT AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) with baseline renal function and follow-up data were included (N=9019). CKD was defined as an estimated creatinine clearance

Background Current American College of Cardiology/American Heart Association guidelines suggest that for patients with atrial fibrillation who are at low risk for stroke (CHA2DS2VASc=1) (or women with CHA2DS2VASc=2) a variety of treatment strategies may be considered. However, in clinical practice, patterns of treatment in these "low-risk" patients are not well described. The objective of this analysis is to define thromboembolic event rates and to describe treatment patterns in patients with low-risk CHA2DS2VASc scores. Methods and Results We compared characteristics, treatment strategies, and outcomes among patients with a CHA2DS2VASc=0, CHA2DS2VASc=1, females with a CHA2DS2VASc=2, and CHA2DS2VASc ≥2 in ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) I & II. Compared with CHA2DS2VASc ≥2 patients (84.2%), those with a CHA2DS2VASc=0 (60.3%), 1 (69.9%), and females with a CHA2DS2VASc score=2 (72.4%) were significantly less often treated with oral anticoagulation ( P

Background Current American College of Cardiology/American Heart Association guidelines suggest that for patients with atrial fibrillation who are at low risk for stroke (CHA2DS2VASc=1) (or women with CHA2DS2VASc=2) a variety of treatment strategies may be considered. However, in clinical practice, patterns of treatment in these "low-risk" patients are not well described. The objective of this analysis is to define thromboembolic event rates and to describe treatment patterns in patients with low-risk CHA2DS2VASc scores. Methods and Results We compared characteristics, treatment strategies, and outcomes among patients with a CHA2DS2VASc=0, CHA2DS2VASc=1, females with a CHA2DS2VASc=2, and CHA2DS2VASc ≥2 in ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) I & II. Compared with CHA2DS2VASc ≥2 patients (84.2%), those with a CHA2DS2VASc=0 (60.3%), 1 (69.9%), and females with a CHA2DS2VASc score=2 (72.4%) were significantly less often treated with oral anticoagulation ( P

Anxiety and depression are associated with worse outcomes in several cardiovascular conditions, but it is unclear whether they affect outcomes in atrial fibrillation (AF). In a large diverse population of adults with AF, we evaluated the association of diagnosed anxiety and/or depression with stroke and bleeding outcomes. The Cardiovascular Research Network WAVE (Community-Based Control and Persistence of Warfarin Therapy and Associated Rates and Predictors of Adverse Clinical Events in Atrial Fibrillation and Venous Thromboembolism) Study included adults with AF newly starting warfarin between 2004 and 2007 within 5 health delivery systems in the United States. Diagnosed anxiety and depression and other patient characteristics were identified from electronic health records. We identified stroke and bleeding outcomes from hospitalization databases using validated International Classification of Diseases, Ninth Revision (ICD-9), codes. We used multivariable Cox regression to assess the relation between anxiety and/or depression with outcomes after adjustment for stroke and bleeding risk factors. In 25 570 adults with AF initiating warfarin, 490 had an ischemic stroke or intracranial hemorrhage (1.52 events per 100 person-years). In multivariable analyses, diagnosed anxiety was associated with a higher adjusted rate of combined ischemic stroke and intracranial hemorrhage (hazard ratio, 1.52; 95% confidence interval, 1.01-2.28). Results were not materially changed after additional adjustment for patient-level percentage of time in therapeutic anticoagulation range on warfarin (hazard ratio, 1.56; 95% confidence interval, 1.03-2.36). In contrast, neither isolated depression nor combined depression and anxiety were significantly associated with outcomes. Diagnosed anxiety was independently associated with increased risk of combined ischemic stroke and intracranial hemorrhage in adults with AF initiating warfarin that was not explained by differences in risk factors or achieved anticoagulation quality.

BackgroundDiagnosed diabetes mellitus (DM) is a consistently documented risk factor for ischemic stroke in patients with atrial fibrillation (AF).ObjectivesThe purpose of this study was to assess the association between duration of diabetes and elevated hemoglobin A1c (HbA1c) with risk of stroke among diabetic patients with AF.MethodsWe assessed this association in the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) California community-based cohort of AF patients (study years 1996 to 2003) where all events were clinician adjudicated. We used Cox proportional hazards regression to estimate the rate of ischemic stroke in diabetic patients according to time-varying measures of estimated duration of diabetes (≥3 years compared with

IntroductionRoutine testing for thrombophilia following venous thromboembolism (VTE) is controversial. The use of large datasets to study the clinical impact of thrombophilia testing on patterns of care and patient outcomes may enable more efficient analysis of this practice in a wide range of settings. We set out to examine how accurately algorithms using International Classification of Diseases 9th Revision (ICD-9) codes and/or pharmacy data reflect laboratory-confirmed thrombophilia diagnoses.Materials and methodsA random sample of adult Kaiser Permanente Colorado patients diagnosed with unprovoked VTE between 1/2004 and 12/2010 underwent medical record abstraction of thrombophilia test results. Algorithms using "ICD-9" (positive if a thrombophilia ICD-9 code was present), "Extended anticoagulation (AC)" (positive if AC therapy duration was >6 months), and "ICD-9 & Extended AC" (positive for both) criteria to identify possible thrombophilia cases were tested. Using positive thrombophilia laboratory results as the gold standard, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value of each algorithm were calculated, along with 95% confidence intervals (CIs).ResultsIn our cohort of 636 patients, sensitivities were low (

Selective serotonin reuptake inhibitor (SSRI) medications have been linked to increased bleeding risk; however, the actual association among warfarin, SSRI exposure, and bleeding risk has not been well-established. We studied the AnTicoagulation and Risk factors In Atrial fibrillation cohort of 13,559 adults with atrial fibrillation, restricted to the 9,186 patients contributing follow-up time while taking warfarin. Exposure to SSRIs and tricyclic antidepressants (TCAs) was assessed from pharmacy database dispensing data. The main outcome was hospitalization for major hemorrhage. Results were adjusted for bleeding risk and time in international normalized ratio range >3. We identified 461 major hemorrhages during 32,888 person-years of follow-up, 45 events during SSRI use, 12 during TCA-only use, and 404 without either medication. Hemorrhage rates were higher during periods of SSRI exposure compared with periods on no antidepressants (2.32 per 100 person-years vs 1.35 per 100 person-years, p 3, SSRI exposure was associated with an increased rate of hemorrhage compared with no antidepressants (adjusted relative risk 1.41, 95% confidence interval 1.04 to 1.92, p = 0.03), whereas TCA exposure was not (adjusted relative risk 0.82, 95% confidence interval 0.46 to 1.46, p = 0.50). In conclusion, SSRI exposure was associated with higher major hemorrhage risk in patients taking warfarin, and this risk should be considered when selecting antidepressant treatments in those patients.

BackgroundPhysicians treating patients with atrial fibrillation (AF) must weigh the benefits of anticoagulation in preventing stroke versus the risk of bleeding. Although empirical models have been developed to predict such risks, the degree to which these coincide with clinicians' estimates is unclear.Methods and resultsWe examined 10 094 AF patients enrolled in the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF) registry between June 2010 and August 2011. Empirical stroke and bleeding risks were assessed by using the congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and previous stroke or transient ischemic attack (CHADS2) and Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) scores, respectively. Separately, physicians were asked to categorize their patients' stroke and bleeding risks: low risk (6%). Overall, 72% (n=7251) in ORBIT-AF had high-risk CHADS2 scores (≥2). However, only 16% were assessed as high stroke risk by physicians. Although 17% (n=1749) had high ATRIA bleeding risk (score ≥5), only 7% (n=719) were considered so by physicians. The associations between empirical and physician-estimated stroke and bleeding risks were low (weighted Kappa 0.1 and 0.11, respectively). Physicians weighed hypertension, heart failure, and diabetes mellitus less significantly than empirical models in estimating stroke risk; physicians weighted anemia and dialysis less significantly than empirical models when estimating bleeding risks. Anticoagulation use was highest among patients with high stroke risk, assessed by either empirical model or physician estimates. In contrast, physician and empirical estimates of bleeding had limited impact on treatment choice.ConclusionsThere is little agreement between provider-assessed risk and empirical scores in AF. These differences may explain, in part, the current divergence of anticoagulation treatment decisions from guideline recommendations.Clinical trial registration urlhttp://www.clinicaltrials.gov. Unique identifier: NCT01165710.

Purpose of reviewAtrial fibrillation is the most common sustained arrhythmia in patients with kidney disease. The purpose of this review is to describe the burden of atrial fibrillation in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD), postulate possible mechanisms to explain this burden of disease, understand the clinical consequences of atrial fibrillation and review the treatment options for atrial fibrillation specific to patients with kidney disease.Recent findingsRecent literature has revealed that the clinical multiorgan impact of atrial fibrillation in patients with CKD and ESRD is substantial. Although novel oral anticoagulants to treat atrial fibrillation and prevent associated complications have been tested in large trials in the general population, there is a paucity of data on the efficacy and safety of these agents in patients with advanced CKD and ESRD.SummaryAtrial fibrillation is a significant comorbidity in patients with CKD and ESRD with important prognostic implications. More research is needed to understand the mechanisms that contribute to the disproportionate burden of this arrhythmia in patients with kidney disease and in to treatment options specific to this population of high-risk patients.