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There are limited data about the frequency of urgent surgical emergencies among patients receiving oral anticoagulants (OACs). We conducted a systematic literature review of Medline and EMBASE for published English-language articles of adult patients receiving oral anticoagulant treatment (vitamin K antagonists, apixaban, dabigatran, edoxaban, rivaroxaban) that reported on patients experiencing unplanned emergent or urgent surgery/procedure or trauma. Randomized trials, observational studies, and case series (50-100 cases) were included. The primary outcome was the frequency of unplanned urgent surgery or invasive procedures among OAC-treated patients with a focus on those not precipitated by the presence of major bleeding. The protocol was not registered. Funding was provided by Covis Pharmaceuticals. The search yielded 1367 potential studies of which 34 were included in the final review. One study reported the rate of urgent surgery/procedures among a large cohort of patients treated with dabigatran or warfarin for atrial fibrillation (~ 1% per year). Another study reported the rate of bleeding or urgent surgery among OAC-treated patients experiencing a fracture or trauma (0.489% per patient-year). The remaining 32 studies were cohorts of OAC-treated patients who received reversal or hemostatic therapies for major bleeding or urgent surgery. A median of 28.8% of these patients underwent surgery or invasive procedure. Urgent surgery appears to be a common, yet understudied complication during OAC treatment potentially associated with high rates of adverse outcomes. With increased eligibility for OACs, future studies evaluating the management and outcomes in this setting are needed., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

While oral anticoagulation is a cornerstone of stroke prevention therapy in atrial fibrillation (AF), few studies have evaluated comparative discontinuation rates in clinical practice. The objective of this study is to evaluate discontinuation rates among patients on warfarin and direct oral anticoagulants (DOACs) in clinical practice., Methods: The ORBIT-AF II Registry enrolled 10,005 total AF patients with a CHA 2 DS 2 VASc score of ≥2 on warfarin or DOACs from 235 clinical practices across the US from February 13, 2013 and July 12, 2017. Descriptive statistics and multivariable Cox regression modeling were used to describe baseline characteristics and predictors of discontinuation. Unadjusted and adjusted discontinuation rates and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and propensity score adjustment, respectively., Results: At baseline, 16.4% (N = 1642/10,005) were treated with warfarin, 83.6% (N = 8363/10,005) with DOACs and 1498/10,005 patients (15.0%) discontinued therapy [warfarin = 236/1642 (14.4%) vs DOACs = 1262/8363 (15.1%)]. At 6 and 12 months respectively, among 7049 patients with a new diagnosis of AF within 6 months, adjusted discontinuation rates for warfarin versus DOACs were as follows: [6 months: 7.9%, 95%CI (6.8%-9.0%) vs 9.6% (8.4%-10.7%), P = .16]; [12 months: 12.7% (11.0%-14.3%) vs 15.3% (13.6%-16.9%), P = .02)]. Patients who discontinued therapy with warfarin or DOACs had higher risk of adverse clinical outcomes including: all-cause mortality and cardiovascular death (CV) than those who continued treatment., Conclusion: In a community based AF cohort, adjusted rates of discontinuation at 12-months were higher in DOAC-treated versus VKA-treated patients. Discontinuation of oral anticoagulation was associated with increased absolute risk of all-cause mortality and CV death., Clinical Trial Registration: URL:https://clinicaltrials.gov. Unique Identifier: NCT01701817., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Patients with atrial fibrillation on oral anticoagulation (OAC) undergoing cardiac catheterization face risks for embolic and bleeding events, yet information on strategies to mitigate these risks in contemporary practice is lacking., Methods: We aimed to describe the clinical/procedural characteristics of a contemporary cohort of patients with atrial fibrillation on OAC who underwent cardiac catheterization. Use of bleeding avoidance strategies and bridging therapy were described and outcomes including death, stroke, and major bleeding at 30 days and 1 year were compared by OAC type., Results: Of 13 404 patients in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II Registry from 2013 to 2016, 741 underwent cardiac catheterization (139 with percutaneous coronary intervention) in the setting of OAC. The patients' median age was 71, 61.8% were male, white (87.2%), had hypertension (83.7%), hyperlipidemia (72.1%), diabetes mellitus (31.6%), and chronic kidney disease (28.2%); 20.2% received warfarin while 79.8% received direct acting oral anticoagulant. One third of patients underwent radial artery access, and bivalirudin was used in 4.6%. Bridging therapy was used more often in patients on warfarin versus direct acting oral anticoagulant (16.7% versus10.0%). OAC was interrupted in 93.8% of patients. Patients on warfarin versus direct acting oral anticoagulant were equally likely to restart OAC (58.0% versus 60.7%), had similar use of antiplatelet therapy (44.0% versus 41.3%) after catheterization, and had similar rates of myocardial infarction and death at 1 year, but higher rates of major bleeding (43.3 versus 12.9 events/100 patient years) and stroke (4.9 versus 1.9 events/100 patient years)., Conclusions: In a real-world registry of patients with atrial fibrillation undergoing cardiac catheterization, most cases are elective, performed by femoral access, with interruption of OAC. Bleeding avoidance strategies such as radial artery access and bivalirudin were used infrequently and use of bridging therapy was uncommon. Nearly 40% of patients did not restart OAC postprocedure, exposing patients to risk for stroke. Further research is necessary to optimize the management of patients with atrial fibrillation undergoing cardiac catheterization.

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: The incidence of cognitive impairment and frailty increase with age and may impact both therapy and outcomes in atrial fibrillation (AF)., Methods: We examined the prevalence of clinically recognized cognitive impairment and frailty (as defined by the American Geriatric Society Criteria) in the Outcomes Registry for Better Informed Care in AF (ORBIT AF) and associated adjusted outcomes via multivariable Cox regression. The interaction between cognitive impairment and frailty and oral anticoagulation (OAC) in determining outcomes was examined., Results: Among 9749 patients with AF [median (IQR) age 75 (67-82) y, 57% male], cognitive impairment and frailty was identified in 293 (3.0%) and 575 (5.9%) patients respectively. Frail patients (68 vs 77%, P < .001) and those with cognitive impairment (70 vs 77%, P = .006) were both less likely to receive an OAC. Both cognitive impairment [HR (95% CI) 1.34 (1.05-1.72), P = .0198] and frailty [HR 1.29 (1.08-1.55), P = .0060] were associated with increased risk of death. Cognitive impairment and frailty were not associated with stroke/transient ischemic attack (TIA) or major bleeding. In multivariable analysis, there was no interaction between OAC use and cognitive impairment or frailty in their associations with mortality, major bleeding and a composite end point of stroke, non-central nervous system systemic embolism, TIA, myocardial infarction or cardiovascular death., Conclusion: Those with cognitive impairment or frailty in AF had higher predicted risk for stroke and higher observed mortality, yet were less likely to be treated with OAC. Despite this, the benefits of OAC were similar in patients with and without cognitive impairment or frailty., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The direct oral anticoagulants (DOACs) currently require no monitoring for routine therapy of atrial fibrillation or venous thromboembolism. Measurement of activity, however, may be important in patients with major and life-threatening bleeding, patients needing emergent surgery, in reversal situations, or in patients at high risk of bleeding or thrombosis due to underlying conditions. For these patients, a widely available and rapid turnaround assay would be optimal. To date, there is no such assay available, especially for the direct factor Xa inhibitors. This report describes the performance of a new, rapid turnaround, point-of-care (PoC) assay for measuring the activity of a range of anticoagulants, including DOACs and heparins, in emergency situations and for routine measurement in high-risk patients. Perosphere Technologies' PoC coagulometer is a handheld instrument that performs individual coagulation tests on samples of fresh whole blood (∼10 µL) with clotting activated by glass contact and endpoint determination performed by infrared spectroscopy. In preclinical studies using rats anticoagulated with therapeutic doses of edoxaban or enoxaparin, the PoC coagulometer showed a strong linear correlation between pharmacokinetic parameters and clotting time with edoxaban ( r 2  = 0.994) and with enoxaparin ( r 2  = 0.967). These preclinical results suggest that this PoC coagulometer would be ideal to assess the pharmacodynamic effects of anticoagulants and their reversal agents. The PoC bedside instrument delivers results within minutes and requires no more than a drop of whole blood. Studies are underway to confirm these results in humans and to further characterize the performance of the instrument., Competing Interests: Dr. Jiang reports personal fees from Perosphere Pharmaceuticals, during the conduct of the study; personal fees from Perosphere Pharmaceuticals, outside the submitted work.Dr. Laulicht reports personal fees from Perosphere Pharmaceuticals Inc., during the conduct of the study; personal fees from Perosphere Pharmaceuticals Inc., outside the submitted work; in addition, Dr. Laulicht has a patent US20160069913A1 issued.Dr. Zappe reports personal fees from Perosphere Technologies, during the conduct of the study; personal fees from Perosphere Technologies, outside the submitted work; in addition, Dr. Zappe has a patent US20160069913A1 issued.Dr. Steiner reports personal fees from Perosphere Pharmaceuticals Inc., during the conduct of the study.Dr. Bakhru reports personal fees from Perosphere Technologies Inc., during the conduct of the study; personal fees from Perosphere Technologies Inc., outside the submitted work; in addition, Dr. Bakhru has a patent US20160069913A1 issued.Dr. Chen reports personal fees from Perosphere Pharmaceuticals, during the conduct of the study; personal fees from Perosphere Pharmaceuticals, outside the submitted work.Dr. Ansell reports other from Perosphere Pharmaceuticals, outside the submitted work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Renal function has been associated with an increased stroke risk in patients with atrial fibrillation (AF). However, whether renal function incrementally adds to risk prediction in both anticoagulated and non-anticoagulated patients with AF is unclear., Methods: We used data from the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF)-a national, prospective, outpatient AF registry in patients aged >18 years (2010-2011). The association between baseline renal function and risk of stroke/systemic embolism (SSE) was evaluated in proportional hazards models adjusting for stroke risk score components. We compared discrimination of 2-year outcomes using C-indices and evaluated calibration by comparing event rates in ORBIT-AF to published rates from an external clinical trial population (ROCKET AF) and an observational cohort (ATRIA)., Results: Among 9743 patients included in the analysis, the median age was 75 years (interquartile range [IQR] 67-82), 89.5% were white, 43% were female, and 76% were taking oral anticoagulation (OAC). Over a median follow-up of 2.3 years, 214 SSE events occurred (1.00 per 100 patient-years). Continuous creatinine clearance (CrCl) was not associated with SSE risk after adjusting for other clinical factors (components of CHADS 2 or CHA 2 DS 2 -VASc). Discrimination for predicting stroke (C-index; 95% CI) was similar for R 2 CHADS 2 (0.65; 0.61-0.69), CHADS 2 (0.65; 0.61-0.69), and CHA 2 DS 2 -VASc (0.66; 0.62-0.70)., Conclusions and Relevance: In a community patient population with AF, renal dysfunction was not independently associated with embolic risk beyond other established risk factors in either OAC-treated or untreated patients. Additional study is needed to identify clinical factors that incrementally add to stroke risk prediction., (Copyright © 2018. Published by Elsevier B.V.)

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 < .0001]. Predictors of dabigatran persistence included: CHA 2 DS 2 -VASc risk scores ≥ 2 OR 5.69, (95% CI 1.50-21.6) and BMI greater than 25 mg/m 2 but less than 38 kg/m 2 1.05 (1.01-1.09). Predictors of persistence on warfarin included: African American race (vs. White) 1.53 (1.07-2.19), Hispanic ethnicity (vs. White) 1.66 (1.06-2.60), paroxysmal and persistent AF (vs. new-onset) 1.68 (1.21-2.33) and 1.91 (1.35-2.69) respectively, LVH 1.40 (1.08-1.81), and CHA 2 DS 2 -VASc risk scores ≥ 2 1.94 (1.18-3.19). While 1-year persistence rates for dabigatran were lower than warfarin, persistence rates for both agents were not ideal. Future studies evaluating contemporary persistence are needed in order to assist in better targeting interventions aimed to improve anticoagulation persistence.

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 <60 mL /min. Patient characteristics were compared by CKD status, and Cox proportional hazards modeling was used to examine the association between oral anticoagulant ( OAC ) use and outcomes and antiarrhythmic drug use and outcomes stratified by CKD stages. At enrollment, 3490 (39%) patients had an estimated creatinine clearance <60 mL /min. Patients with CKD were older and had higher CHA 2 DS 2 VAS c and Anticoagulant and Risk Factors in Atrial Fibrillation (ATRIA) scores. A rhythm control strategy was selected less frequently in patients with CKD , while OAC use was lower among Stage IV and V CKD patients. After adjustment, no significant interaction was noted for OAC and CKD on all-cause mortality ( P=0.5442) or cardiovascular death ( P=0.1233), although a trend for increased major bleeding ( P=0.0608) and stroke, systemic embolism or transient ischemic attack ( P=0.0671) was observed. No interaction was noted for antiarrhythmic drug use and CKD status on all-cause mortality ( P=0.9706), or stroke, systemic embolism or transient ischemic attack ( P=0.4218). Conclusions Patients with atrial fibrillation and CKD are less likely to be treated with rhythm control. Patients with advanced CKD are less likely to receive OAC . Finally, outcomes with OAC in patients with advanced CKD may be materially different with higher rates of both bleeding and stroke.

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: Oral anticoagulation (OAC) reduces stroke risk in atrial fibrillation, but bleeding is a frequent side effect. The decision to discontinue or modify medication regimens in response to a bleeding event may differ according to bleeding site and severity., Methods and Results: We used data from a large, national outpatient registry, ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation; 2010-2011), to evaluate event characteristics and OAC management following the first bleeding event occurring during follow-up. Bleeding events were classified into 3 categories: (1) International Society of Thrombosis and Hemostasis major bleeding, (2) clinically relevant nonmajor bleeding requiring medical attention, and (3) nuisance bleeding not requiring medical attention (eg, bruising, hemorrhoidal bleeding). Of 9743 patients enrolled in ORBIT-AF with follow-up data, 510 (3.23/100 subject-years) experienced a major bleed, 615 (3.90/100 subject-years), experienced a clinically relevant nonmajor bleed, and 1558 (9.87/100 subject-years) experienced a nuisance bleed, among first bleeds over 2 years. Nearly one third of patients (31.6%) discontinued OAC therapy following a major bleeding event, 12.7% following a clinically relevant nonmajor bleed, and 4.5% following a nuisance bleed. Compared with those who experienced a clinically relevant nonmajor or nuisance bleed, patients who experienced a major bleed were more likely to be black and female and to have a history of heart failure and stroke. Those who discontinued were more likely to have central nervous system or gastrointestinal bleeding than those who persisted on OAC therapy., Conclusions: Overall, 1 in 3 patients who experienced a major bleed was no longer anticoagulated after the event. Those who discontinued OAC were more likely to have central nervous system or gastrointestinal bleeding than those who persisted on OAC., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objective: To describe self-reported disease understanding for newly diagnosed patients with atrial fibrillation (AF) and assess (1) how disease understanding changes over the first 6 months after diagnosis and (2) the relationship between patient understanding of therapies at baseline and treatment receipt at 6 months among treatment-naïve patients., Methods: We analysed survey data from SATELLITE (Survey of Patient Knowledge and Personal Priorities for Treatment), a substudy of patients with new-onset AF enrolled in the national Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT) II registry across 56 US sites. Patients were surveyed at the baseline and 6-month follow-up clinic visits using Likert scales., Results: Among 1004 baseline survey responses, patients' confidence in their understanding of rhythm control, ablation, anticoagulation and cardioversion was suboptimal, with 'high' understanding ranging from 8.5% for left atrial appendage closure to 71.3% for rhythm therapy. Of medical history and demographic factors, education level was the strongest predictor of reporting 'high' disease understanding. Among the 786 patients with 6-month survey data, significant increases in the proportion reporting high understanding were observed (p<0.05) only for warfarin and direct oral anticoagulants (DOACs). With the exception of ablation, high understanding for a given therapeutic option was not associated with increased use of that therapy at 6 months., Conclusions: About half of patients with new-onset AF understood the benefits of oral anticoagulant at the time of diagnosis and understanding improved over the first 6 months. However, understanding of AF treatment remains suboptimal at 6 months. Our results suggest a need for ongoing patient education., Clinical Trial Registration: Clinicaltrials.gov. Identifier: NCT01701817., Competing Interests: Competing interests: BGK, SK and KP: None. LAA: consultancy from Novartis (significant) and Janssen. JP: significant research support from Boston Scientific, ResMed, ARCA Biopharma, St. Jude Medical Center, Gilead Sciences, Johnson&Johnson, Spectranetics and Janssen and consultancies to Janssen (significant), Spectranetics (significant), Medtronic (significant), Forest Laboratories (modest), Pfizer (modest) and GlaxoSmithKline (modest). EP: significant research support from Eli Lilly & Company, Daiichi Sankyo and Janssen. ECO: significant research grant from Janssen, BMS, Novartis and Pfizer. BJG: consultancies to Janssen Scientific Affairs (significant) and Cipla Limited Data Safety Monitoring Board (modest) for: Mount Sinai St. Lukes, Boston Scientific Corporation, Teva Pharmaceutical Industries, St. Jude Medical, Janssen Research & Development, Baxter Healthcare Corporation, Thrombosis Research Institute, Duke Clinical Research Institute, Duke University, Kowa Research Institute and Cardiovascular Research Foundation. PRK: consultant to Johnson&Johnson (significant). GCF: consultant to Janssen (modest). JAR: consultant and/or speaker’s bureau for Boehringer-Ingelheim, Janssen (significant), Pfizer, BMS, Portola (modest) and Daiichi Sankyo. JVF: consultant to Janssen (modest) and salary support from the American College of Cardiology National Cardiovascular Data Registry. JA: consultancy/advisory board to Bristol-Myers Squibb; Pfizer; Janssen; Daiichi Sankyo; Boehringer Ingelheim; Instrumentation Laboratories; Perosphere; Roche Diagnostics. Equity in Perosphere. MDE: consultancies to Boehringer Ingelheim and Daiichi Sankyo (modest) and Bristol-Myers Squibb, Pfizer, Johnson&Johnson and Janssen Scientific Affairs (significant). GVN: consultant/advisory board to Janssen, Daiichi Sankyo, GlaxoSmithKline, Astra Zeneca; research support from Janssen. PSC: funding from the NHLBI (1R01HL123980). DES: consultant/advisory board to Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Johnson&Johnson, Medtronic, Pfizer; research grants from Boehringer Ingelheim, Bristol-Myers Squibb and Medtronic. KWM: financial disclosures can be viewed at http://med.stanford.edu/profiles/kenneth-mahaffey., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) are indicated for stroke prevention in atrial fibrillation (AF) but require lower doses in certain patients. We sought to describe the frequency, appropriateness (according to Food and Drug Administration labeling), and outcomes of patients prescribed reduced doses of NOACs in community practice., Methods and Results: We analyzed data from the ORBIT-AF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II) registry, a prospective, national, observational registry of AF patients. Among 7925 AF patients receiving NOACs, we assessed patterns of use of reduced NOAC doses and associated cardiovascular and bleeding outcomes at median follow-up of 1 year. Overall, 6636 patients (84%) received a NOAC at standard dose, which was consistent with US Food and Drug Administration labeling in 6376 (96%). Reduced NOAC dose was prescribed to 1289 (16% overall), which was consistent with Food and Drug Administration labeling in only 555 patients (43%). Compared with those whose NOAC dose was appropriately reduced, patients receiving inappropriate dose reductions were younger (median age 79 versus 84, P <0.0001) and had lower ORBIT bleeding risk scores (26% ≥4 versus 45%, P <0.0001). Compared with those appropriately receiving standard dosing, patients receiving inappropriately reduced-dose NOACs had higher unadjusted rates of thromboembolic events (2.11 versus 1.35 events per 100 patient years, hazard ratio 1.56, 95% confidence interval 0.92-2.67) and death (6.77 versus 2.60, hazard ratio 2.61, 95% confidence interval 1.86-3.67). After adjustment, outcomes were not significantly different but tended to favor patients dosed appropriately., Conclusions: The majority of dose reductions of NOACs in AF are inconsistent with US Food and Drug Administration recommendations. There appear to be opportunities to improve current NOAC dosing in community practice., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01701817., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: The presence of valvular heart disease (VHD) may affect the risk of stroke and mortality in patients with atrial fibrillation (AF). Community-based estimates of prevalence and outcomes of specific forms of VHD in patients with AF are lacking., Methods and Results: We examined the prevalence of VHD, anticoagulation use, mortality, stroke/transient ischemic attack, and bleeding among a community cohort of patients with AF. Significant VHD was defined as follows: (1) moderate/severe mitral stenosis or mechanical valve; (2) bioprosthetic valve, surgical repair, or balloon valvuloplasty; and (3) moderate/severe aortic regurgitation or stenosis, mitral regurgitation, or tricuspid regurgitation. Proportional hazards models were performed to test the association between VHD groups and outcomes. Among 9748 patients with AF, 2705 (27.7%) had significant VHD. Anticoagulation use was highest among patients with mitral stenosis/mechanical valve (91.8%). Compared with individuals with no significant VHD, individuals with aortic regurgitation/aortic stenosis, mitral regurgitation, or tricuspid regurgitation (hazard ratio, 1.23; 95% confidence interval, 1.07-1.42) had the highest risk of death. There were no differences in stroke or transient ischemic attack and major bleeding among individuals with and without significant VHD. Patients with AF and aortic stenosis had the highest risk of death (hazard ratio, 1.32; 95% confidence interval, 1.08-1.62)., Conclusions: Significant VHD is common among patients with AF in community practice. In a community cohort of patients with AF and CHA 2 DS 2 -VASc score ≥2, most were anticoagulated. Individuals with AF and moderate-to-severe biological VHD have more comorbidities and a higher mortality risk; however, stroke and major bleeding are similar among those with and without significant VHD., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world. We aimed to provide comprehensive data on international patterns of AF stroke prevention treatment., Methods: Demographics, comorbidities, and stroke risk of the patients in the GARFIELD-AF (n=51,270), ORBIT-AF I (n=10,132), and ORBIT-AF II (n=11,602) registries were compared (overall N=73,004 from 35 countries). Stroke prevention therapies were assessed among patients with new-onset AF (≤6 weeks)., Results: Patients from GARFIELD-AF were less likely to be white (63% vs 89% for ORBIT-AF I and 86% for ORBIT-AF II) or have coronary artery disease (19% vs 36% and 27%), but had similar stroke risk (85% CHA 2 DS 2 -VASc ≥2 vs 91% and 85%) and lower bleeding risk (11% with HAS-BLED ≥3 vs 24% and 15%). Oral anticoagulant use was 46% and 57% for patients with a CHA 2 DS 2 -VASc=0 and 69% and 87% for CHA 2 DS 2 -VASc ≥2 in GARFIELD-AF and ORBIT-AF II, respectively, but with substantial geographic heterogeneity in use of oral anticoagulant (range: 31%-93% [GARFIELD-AF] and 66%-100% [ORBIT-AF II]). Among patients with new-onset AF, non-vitamin K antagonist oral anticoagulant use increased over time to 43% in 2016 for GARFIELD-AF and 71% for ORBIT-AF II, whereas use of antiplatelet monotherapy decreased from 36% to 17% (GARFIELD-AF) and 18% to 8% (ORBIT-AF I and II)., Conclusions: Among new-onset AF patients, non-vitamin K antagonist oral anticoagulant use has increased and antiplatelet monotherapy has decreased. However, anticoagulation is used frequently in low-risk patients and inconsistently in those at high risk of stroke. Significant geographic variability in anticoagulation persists and represents an opportunity for improvement., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: It is unclear how frequently patients with atrial fibrillation receive guideline-concordant (GC) care and whether guideline concordance is associated with improved outcomes., Methods and Results: Using data from ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation), we determined how frequently patients received care that was concordant with 11 recommendations from the 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society atrial fibrillation guidelines pertaining to antithrombotic therapy, rate control, and antiarrhythmic medications. We also analyzed the association between GC care and clinical outcomes at both the patient level and center level. A total of 9570 patients were included. The median age was 75 years (interquartile range, 67-82), and the median CHA 2 DS 2 -VASc score was 4 (interquartile range, 3-5). A total of 5977 patients (62.5%) received care that was concordant with all guideline recommendations for which they were eligible. Rates of GC care were higher in patients treated by providers with greater specialization in arrhythmias (60.0%, 62.4%, and 67.0% for primary care physicians, cardiologists, and electrophysiologists, respectively; P <0.001). During a median of 30 months of follow-up, patients treated with GC care had a higher risk of bleeding hospitalization (hazard ratio=1.21; P =0.021) but a similar risk of death, stroke, major bleeding, and all-cause hospitalization., Conclusions: Over a third of patients with atrial fibrillation in this large outpatient registry received care that differed in some respect from guideline recommendations. There was no apparent association between GC care and improved risk-adjusted outcomes., (© 2017 American Heart Association, Inc.)

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.)

Background: Several non-vitamin K antagonist oral anticoagulant (NOAC) alternatives to warfarin are available for stroke prevention in atrial fibrillation (AF). We aimed to describe the factors associated with selection of NOACs versus warfarin in patients with new onset AF., Methods: The ORBIT-AF II study is a national, US, prospective, observational, cohort study of anticoagulation treatment in patients with AF receiving NOACs or warfarin in the United States from 2013 to 2016. We measured factors associated with oral anticoagulant selection in 4,670 patients recently diagnosed with AF., Results: At baseline, 1,169 (25%) patients were started on warfarin and 3,501 (75%) on NOACs: of these latter, 259 (6%) were started on dabigatran, 1858 (40%) on rivaroxaban, and 1384 (30%) on apixaban. Those receiving NOACs were slightly younger patients (median age 71 vs 72, P<.0001); were less likely to have prior stroke (5.3% vs 8.6%; P<.0001) or prior bleeding (2.7% vs 4.4%; P=.005); had better kidney function (mean estimated glomerular filtration rate 91 mL/min vs 80 mL/min, P<.0001); and had fewer patients at high stroke risk (CHA 2 DS 2 -VASc score [Congestive heart failure, Hypertension, Age ≥75years, Diabetes mellitus, Prior stroke, transient ischemic attack {TIA}, or thromboembolism,Vascular disease, Age 65-74years, Sex category {female}] ≥2 in 86% vs 93%; P<.0001). In multivariable analysis, factors associated with NOAC selection versus warfarin included renal function, prior stroke or valve replacement, rhythm control AF management strategy, treatment by a cardiologist, and higher patient education level., Conclusions: In contemporary clinical practice, up to three-fourths of patients with new-onset AF are now initially treated with a NOAC for stroke prevention. Those selected for NOAC treatment had lower stroke and bleeding risk profiles, were more likely treated by cardiologists, and had higher socioeconomic status., Trial Registration: clinicaltrials.gov Identifier: NCT01701817., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

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.)

Non-vitamin K antagonist oral anticoagulants (NOACs) are effective at preventing stroke in patients with atrial fibrillation (AF). However, little is known about the management of bleeding in contemporary, clinical use of NOACs. We aimed to assess the frequency, management, and outcomes of major bleeding in the setting of community use of NOACs. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry, we analyzed rates of International Society on Thrombosis and Haemostasis major bleeding and subsequent outcomes in patients treated with NOACs versus warfarin. Outcomes of interest included acute and chronic bleeding management, recurrent bleeding, thromboembolic events, and death. In total, 344 patients with atrial fibrillation experienced major bleeding events over a median follow-up of 360 days follow-up: n = 273 on NOAC (3.3 per 100 patient-years) and n = 71 on warfarin (3.5 per 100 patient-years). Intracranial bleeding was uncommon but similar (0.34 per 100 patient-years for NOAC vs 0.44 for warfarin, p = 0.5), as was gastrointestinal bleeding (1.8 for NOAC vs 1.3 for warfarin, p = 0.1). Blood products and correction agents were less commonly used in NOAC patients with major bleeds compared with warfarin-treated patients (53% vs 76%, p = 0.0004 for blood products; 0% vs 1.5% for recombinant factor; p = 0.0499); no patients received pharmacologic hemostatic agents (aminocaproic acid, tranexamic acid, desmopressin, aprotinin). Within 30 days, 23 NOAC-treated patients (8.4%) died versus 5 (7.0%) on warfarin (p = 0.7). At follow-up, 126 NOAC-treated (46%) and 29 warfarin-treated patients (41%) were not receiving any anticoagulation. In conclusion, rates of major bleeding are similar in warfarin and NOAC-treated patients in clinical practice. However, NOAC-related bleeds require less blood product administration and rarely require factor replacement., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial reported that apixaban therapy was superior to warfarin therapy in preventing stroke and all-cause death while causing significantly fewer major bleeds. To establish the value proposition of substituting apixiban therapy for warfarin therapy in patients with atrial fibrillation, we performed a cost-effectiveness analysis using patient-level data from the ARISTOTLE trial., Objective: To assess the cost and cost-effectiveness of apixaban therapy compared with warfarin therapy in patients with atrial fibrillation from the perspective of the US health care system., Design, Setting, and Participants: This economic analysis uses patient-level resource use and clinical data collected in the ARISTOTLE trial, a multinational randomized clinical trial that observed 18 201 patients (3417 US patients) for a median of 1.8 years between 2006 and 2011., Interventions: Apixaban therapy vs warfarin therapy., Main Outcomes and Measures: Within-trial resource use and cost were compared between treatments, using externally derived US cost weights. Life expectancies for US patients were estimated according to their baseline risk and treatment using time-based and age-based survival models developed using the overall ARISTOTLE population. Quality-of-life adjustment factors were obtained from external sources. Cost-effectiveness (incremental cost per quality-adjusted life-year gained) was evaluated from a US perspective, and extensive sensitivity analyses were performed., Results: Of the 3417 US patients enrolled in ARISTOTLE, the mean (SD) age was 71 (10) years; 2329 (68.2%) were male and 3264 (95.5%) were white. After 2 years of anticoagulation therapy, health care costs (excluding the study drug) of patients treated with apixaban therapy and warfarin therapy were not statistically different (difference, -$60; 95% CI, -$2728 to $2608). Life expectancy, modeled from ARISTOTLE outcomes, was significantly longer with apixaban therapy vs warfarin therapy (7.94 vs 7.54 quality-adjusted life years). The incremental cost, including cost of anticoagulant and monitoring, of achieving these benefits was within accepted US norms ($53 925 per quality-adjusted life year, with 98% likelihood of meeting a $100 000 willingness-to-pay threshold). Results were generally consistent when model assumptions were varied, with lifetime cost-effectiveness most affected by the price of apixaban and the time horizon., Conclusions and Relevance: Apixaban therapy for ARISTOTLE-eligible patients with atrial fibrillation provides clinical benefits at an incremental cost that represents reasonable value for money judged using US benchmarks for cost-effectiveness., Trial Registration: clinicaltrials.gov Identifier: NCT00412984.

Background: Prior studies have shown a treatment gap in oral anticoagulation (OAC) use among patients with atrial fibrillation yet have incompletely characterized factors associated with failure to treat and subsequent outcomes in contemporary practice., Methods: Using data collected between June 2010 and August 2011 from 174 ambulatory care sites in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we identified factors associated with absence of OAC via stratified logistic regression. Using weighted Cox regression, we assessed the association between OAC non-use and subsequent outcomes over 2.5 years., Results: Among 9553 patients, 2202 (23.0%) were not on OAC. Among OAC nonrecipients, 1846 (83.8%) had a CHA 2 DS 2 -VASc score ≥2. Factors independently associated with OAC non-use included atrial fibrillation type (paroxysmal odds ratio [OR] 0.73, 95% confidence interval [CI] 0.54-0.99; persistent OR 0.14, 95% CI 0.10-0.21; permanent OR 0.35, 95% CI 0.25-0.49; reference = new-onset), left atrial diameter enlargement (mild OR 0.80, 95% CI 0.66-0.97; moderate 0.58, 95% CI 0.47-0.73; severe 0.53, 95% CI 0.42-0.68; reference = normal diameter), and age >80 years (OR 1.04, 95% CI 1.02-1.08). Untreated patients had a higher risk of death (adjusted hazard ratio [HR] 1.22, 95% CI 1.05-1.41), a lower bleeding risk (adjusted HR 0.35, 95% CI 0.15-0.81), and a nonsignificant trend toward higher risk of stroke/non-central nervous system embolism/transient ischemic attack than those treated (adjusted HR 1.18, 95% CI 0.91-1.54)., Conclusions: A majority of atrial fibrillation patients not treated with an OAC in current community practice meet guideline indications for treatment. Atrial fibrillation burden, chronicity, and comorbidity are associated with nontreatment. Untreated patients are at increased risk for adverse outcomes., (Published by Elsevier Inc.)

The choice of oral anticoagulant (OAC) for patients with atrial fibrillation (AF) may be influenced by individual clinical features or by patterns of risk factors and comorbidities. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. non-vitamin K oral anticoagulants (NOACs) for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In addition, we discuss the timing of initiation of anticoagulation. In the second of a two-part review, we discuss the use of NOAC for stroke prevention in the following subgroups of patients with AF: (vii) secondary stroke prevention in patients after stroke or transient ischaemic attack (TIA), (viii) patients with acute stroke requiring thrombolysis or thrombectomy, (ix) those initiating or restarting OAC treatment after stroke or TIA, (x) those with renal impairment on dialysis, (xi) the elderly, (xii) those at high risk of gastrointestinal bleeding, and (xiii) those with hypertension. In addition, we discuss adherence and compliance. Finally, we present a summary of treatment suggestions. In specific subgroups of patients with AF, evidence supports the use of particular NOACs and/or particular doses of anticoagulant. The appropriate choice of treatment for these subgroups will help to promote optimal clinical outcomes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Patients with atrial fibrillation (AF) have a high risk of stroke and mortality, which can be considerably reduced by oral anticoagulants (OAC). Recently, four non-vitamin-K oral anticoagulants (NOACs) were compared with warfarin in large randomized trials for the prevention of stroke and systemic embolism. Today's clinician is faced with the difficult task of selecting a suitable OAC for a patient with a particular clinical profile or a particular pattern of risk factors and concomitant diseases. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. NOACs for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In the first of a two-part review, we discuss the choice of NOAC for stroke prevention in the following subgroups of patients with AF: (i) stable coronary artery disease or peripheral artery disease, including percutaneous coronary intervention with stenting and triple therapy; (ii) cardioversion, ablation and anti-arrhythmic drug therapy; (iii) mechanical valves and rheumatic valve disease, (iv) patients with time in therapeutic range of >70% on warfarin; (v) patients with a single stroke risk factor (CHA2DS2VASc score of 1 in males, 2 in females); and (vi) patients with a single first episode of paroxysmal AF. Although there are no major differences in terms of efficacy and safety between the NOACs for some clinical scenarios, in others we are able to suggest that particular drugs and/or doses be prioritized for anticoagulation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: Although non-vitamin K antagonist oral anticoagulants (NOACs) do not require frequent laboratory monitoring, each compound requires dose adjustments on the basis of certain clinical criteria., Objectives: This study assessed the frequency of off-label NOAC doses among AF patients and the associations between off-label dose therapy and clinical outcomes in community practice., Methods: We evaluated 5,738 patients treated with a NOAC at 242 ORBIT-AF II (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation phase II) sites. NOAC doses were classified as either underdosed or overdosed, consistent with Food and Drug Administration labeling. Longitudinal outcomes (median follow-up: 0.99 years) included stroke or systemic embolism, myocardial infarction, major bleeding (International Society of Thrombosis and Haemostasis criteria), cause-specific hospitalization, and all-cause mortality., Results: Overall, 541 NOAC-treated patients (9.4%) were underdosed, 197 were overdosed (3.4%), and 5,000 were dosed according to U.S. labeling (87%). Compared with patients receiving the recommended dose, those who were receiving off-label doses were older (median: 79 and 80 years of age vs. 70 years of age, respectively; p < 0.0001), more likely female (48% and 67% vs. 40%, respectively; p < 0.0001), less likely to be treated by an electrophysiologist (18% and 19% vs. 27%, respectively; p < 0.0001), and had higher CHA 2 DS 2 -VASc scores (96% and 97% ≥2 vs. 86%, respectively; p < 0.0001) and higher ORBIT bleeding scores (25% and 31% >4 vs. 11%, respectively; p < 0.0001). After dose adjustment, NOAC overdosing was associated with increased all-cause mortality compared with recommended doses (adjusted hazard ratio: 1.91; 95% confidence interval [CI]: 1.02 to 3.60; p = 0.04). Underdosing was associated with increased cardiovascular hospitalization (adjusted hazard ratio: 1.26; 95% CI: 1.07 to 1.50; p = 0.007)., Conclusions: A significant minority (almost 1 in 8) of U.S. patients in the community received NOAC doses inconsistent with labeling. NOAC over- and underdosing are associated with increased risk for adverse events. (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II [ORBIT-AF II]; NCT01701817)., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Assessments of stroke and bleeding risks are essential to selecting oral anticoagulation in patients with atrial fibrillation (AF). We aimed to assess outcomes according to physician assessed risk, with comparison to empirical risk scores., Methods: This was a prospective, observational study of 9,715 outpatients with AF enrolled in ORBIT-AF, a US national registry. Stroke and bleeding risks were quantified by physician assignment, CHADS 2 and CHA 2 DS 2 -VASc stroke scores, and ATRIA and HAS-BLED bleeding scores. Outcomes were stroke or systemic embolism and major bleeding during a median follow-up of 28 months., Results: Physician-assigned risk was associated with thromboembolic events: low risk (0.71 per 100 patient-years [95% CI 0.56-0.91], n=3,991), intermediate risk (0.98 [95% CI 0.79-1.20], n=4,148), and high risk (1.84 [95% CI 1.43-2.37], n=1,576, P<.0001), and major bleeding: low (3.43 [95% CI 3.07-3.82], n=4,250), intermediate (4.55 [95% CI 4.03-5.15], n=2,702), and high (5.76 [95% CI 4.42-7.50], n=468; P<.0001). Discrimination of stroke risk was similar with CHADS 2 (c=0.59, 95% CI 0.57-0.61) vs physician assessment (c=0.58, 95% CI 0.55-0.62). Among patients on oral anticoagulation, bleeding risk discrimination was higher with ATRIA (c=0.63, 95% CI 0.61-0.65) and HAS-BLED (c=0.60, 95% CI 0.59-0.62) than with physician assessment (0.55, 95% CI 0.53-0.57). Physician-assessed risk categories did not add significantly to empirical risk scores, in Cox models for outcomes (P adjusted >.05 for all physician assessments vs P adjusted <.05 for empirical scores)., Conclusion: Physician-assigned risk showed a graded relationship with outcomes, and both physician-based and empirical scores yielded only moderate discrimination. Although empirical scores provided valuable risk stratification information (with or without physician judgment), physician assessment added little to existing scores. These data support the use of empirical scores for stroke and bleeding risk stratification, and the need for novel approaches to risk stratification in this population., (Copyright © 2016 The Authors. Published by 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.)

The North American Thrombosis Forum Atrial Fibrillation Action Initiative consensus document is a comprehensive yet practical briefing document focusing on stroke and bleeding risk assessment in patients with atrial fibrillation, as well as recommendations regarding anticoagulation options and management. Despite the breadth of clinical trial data and guideline recommendation updates, many clinicians continue to struggle to synthesize the disparate information available. This problem slows the uptake and utilization of updated risk prediction tools and adoption of new oral anticoagulants. This document serves as a practical and educational reference for the entire medical community involved in the care of patients with atrial fibrillation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Therapeutic decisions in atrial fibrillation (AF) are often influenced by assessment of bleeding risk. However, existing bleeding risk scores have limitations., Objectives: We sought to develop and validate a novel bleeding risk score using routinely available clinical information to predict major bleeding in a large, community-based AF population., Methods: We analysed data from Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), a prospective registry that enrolled incident and prevalent AF patients at 176 US sites. Using Cox proportional hazards regression, we identified factors independently associated with major bleeding among patients taking oral anticoagulation (OAC) over a median follow-up of 2 years (interquartile range = 1.6-2.5). We also created a numerical bedside risk score that included the five most predictive risk factors weighted according to their strength of association with major bleeding. The predictive performance of the full model, the simple five-item score, and two existing risk scores (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly, drugs/alcohol concomitantly, HAS-BLED, and anticoagulation and risk factors in atrial fibrillation, ATRIA) were then assessed in both the ORBIT-AF cohort and a separate clinical trial population, Rivaroxaban Once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET-AF)., Results: Among 7411 ORBIT-AF patients taking OAC, the rate of major bleeding was 4.0/100 person-years. The full continuous model (12 variables) and five-factor ORBIT risk score (older age [75+ years], reduced haemoglobin/haematocrit/history of anaemia, bleeding history, insufficient kidney function, and treatment with antiplatelet) both had good ability to identify those who bled vs. not (C-index 0.69 and 0.67, respectively). These scores both had similar discrimination, but markedly better calibration when compared with the HAS-BLED and ATRIA scores in an external validation population from the ROCKET-AF trial., Conclusions: The five-element ORBIT bleeding risk score had better ability to predict major bleeding in AF patients when compared with HAS-BLED and ATRIA risk scores. The ORBIT risk score can provide a simple, easily remembered tool to support clinical decision making., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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.)

Aim: In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban., Methods and Results: Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time to event [death, ischaemic stroke, or myocardial infarction (MI)] was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 patients with an ICH, 76 (43.2%) died, and of the 695 patients with major non-ICH, 64 (9.2%) died within 30 days of the bleeding. The risk of death, ischaemic stroke, or MI was increased roughly 12-fold after a major non-ICH bleeding event within 30 days. Corresponding risk of death following an ICH was markedly increased, with HR 121.5 (95% CI 91.3-161.8) as was stroke or MI with HR 21.95 (95% CI 9.88-48.81), respectively. Among patients with major bleeds, 20.8% received vitamin K and/or related medications (fresh frozen plasma, coagulation factors, factor VIIa) to stop bleeding within 3 days, and 37% received blood transfusion. There was no interaction between apixaban and warfarin and major bleeding on the risk of death, stroke, or MI., Conclusion: Major bleeding was associated with substantially increased risk of death, ischaemic stroke, or MI, especially following ICH, and this risk was similarly elevated regardless of treatment with apixaban or warfarin. These results underscore the importance of preventing bleeding in anti-coagulated patients. ClinicalTrials.gov Identifier: NCT00412984., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: Temporary interruption of oral anticoagulation for procedures is often required, and some propose using bridging anticoagulation. However, the use and outcomes of bridging during oral anticoagulation interruptions in clinical practice are unknown., Methods and Results: The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry is a prospective, observational registry study of US outpatients with atrial fibrillation. We recorded incident temporary interruptions of oral anticoagulation for a procedure, including the use and type of bridging therapy. Outcomes included multivariable-adjusted rates of myocardial infarction, stroke or systemic embolism, major bleeding, cause-specific hospitalization, and death within 30 days. Of 7372 patients treated with oral anticoagulation, 2803 overall interruption events occurred in 2200 patients (30%) at a median follow-up of 2 years. Bridging anticoagulants were used in 24% (n=665), predominantly low-molecular-weight heparin (73%, n=487) and unfractionated heparin (15%, n=97). Bridged patients were more likely to have had prior cerebrovascular events (22% versus 15%; P=0.0003) and mechanical valve replacements (9.6% versus 2.4%; P<0.0001); however, there was no difference in CHA2DS2-VASc scores (scores ≥ 2 in 94% versus 95%; P=0.5). Bleeding events were more common in bridged than nonbridged patients (5.0% versus 1.3%; adjusted odds ratio, 3.84; P<0.0001). The incidence of myocardial infarction, stroke or systemic embolism, major bleeding, hospitalization, or death within 30 days was also significantly higher in patients receiving bridging (13% versus 6.3%; adjusted odds ratio, 1.94; P=0.0001)., Conclusions: Bridging anticoagulation is used in one quarter of anticoagulation interruptions and is associated with higher risk for bleeding and adverse events. These data do not support the use of routine bridging, and additional data are needed to identify best practices concerning anticoagulation interruptions., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT01165710., (© 2014 The Authors.)

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: Physicians 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 Results: We 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 (<3%); intermediate risk (3%-6%); and high 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., Conclusions: There 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 Url: http://www.clinicaltrials.gov. Unique identifier: NCT01165710., (© 2014 American Heart Association, Inc.)

Background: Atrial fibrillation (AF) is the most common cardiac dysrhythmia and contributes significantly to health care expenditures. We sought to assess the frequency and predictors of hospitalization in patients with AF., Methods: The ORBIT-AF registry is a prospective, observational study of outpatients with AF enrolled from June 29, 2010, to August 9, 2011. The current analysis included 9,484 participants with 1-year follow-up. Multivariable, logistic regression was used to identify baseline characteristics that were associated with first cause-specific hospitalization., Results: Overall, 31% of patients with AF studied (n = 2,963) had 1 or more hospitalizations per year and 10% (n = 983) had 2 or more. The most common hospitalization cause was cardiovascular (20 per 100 patient-years vs 3.3 bleeding vs 17 noncardiovascular, nonbleeding). Compared with those not hospitalized, hospitalized patients were more likely to have concomitant heart failure (42% vs 28%, P < .0001), higher mean CHADS2 (1 point for congestive heart failure, hypertension, age ≥75, or diabetes; 2 points for prior stroke or transient ischemic attack) scores (2.5 vs 2.2, P < .0001), and more symptoms (baseline European Heart Rhythm Association class severe symptoms 18% vs 13%, P < .0001). In multivariable analysis, heart failure (adjusted hazard ratio [HR] 1.57 for New York Heart Association III/IV vs none, P < .0001), heart rate at baseline (adjusted HR 1.11 per 10-beats/min increase >66, P < .0001), and AF symptom class (adjusted HR 1.37 for European Heart Rhythm Association severe vs none, P < .0001) were the major predictors of incident hospitalization., Conclusions: Hospitalization is common in outpatients with AF and is independently predicted by heart failure and AF symptoms. Improved symptom control, rate control, and comorbid condition management should be evaluated as strategies to reduce health care use in these patients., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background: Anticoagulation control with warfarin, as assessed by the international normalized ratio (INR), is challenging. Time in the therapeutic range has been inversely correlated with major hemorrhage, thrombosis, and mortality. Quest Diagnostics offers standardized INR laboratory testing services to approximately half of US physician practices. To inform national stroke prevention strategies, we evaluated anticoagulation control in office-based community practices., Methods and Results: We selected individuals with ≥2 months of INR data, INR results of >1.2, and an ICD-9 diagnosis code of atrial fibrillation. Frequency of INR testing and time in the therapeutic range were analyzed by age, sex, length of testing period, number of referred patients per provider, and median household income (based on home ZIP code). We identified 138 319 individuals referred by 37 939 physicians, yielding a total of 2 683 674 INR results. Patients had a mean age of 74 years; 81% were ≥65 years of age, and 55% were ≥75 years of age. The mean time in the therapeutic range was 53.7% overall and improved with time on treatment, increasing from 47.6% for patients with <6 months of testing to 57.5% for those with ≥6 months of testing (P<0.0001). The number of patients tested per physician practice was positively associated with time in the therapeutic range. Younger age, female sex, and lower income were also independently associated with poorer anticoagulant control., Conclusion: This study demonstrates widespread suboptimal anticoagulation control, suggesting an urgent need to improve oral anticoagulation care for most patient segments in the United States.

Background: Oral anticoagulation (OAC) therapy reduces the risk of thromboembolic events associated with atrial fibrillation (AF), yet a substantial proportion of patients with AF are not prescribed OAC. The aim of this study is to describe the frequencies of and factors associated with OAC contraindications in contemporary clinical practice., Methods: We analyzed data from the ORBIT-AF study, a national, prospective, outpatient registry of incident and prevalent AF. Oral anticoagulation contraindications were uniformly collected at enrollment by site personnel using a predefined list. Baseline patient and provider characteristics were compared between participants with and without documented OAC contraindications., Results: From June 2010 to August 2011, 10,130 patients 18 years or older with electrocardiographically documented AF were enrolled at 176 practices. Of these, 1,330 (13.1%) had contraindications documented at the baseline visit: prior bleed (27.7%), patient refusal/preference (27.5%), high bleeding risk (18.0%), frequent falls/frailty (17.6%), need for dual antiplatelet therapy (10.4%), unable to adhere/monitor warfarin (6.0%), comorbid illness (5.3%), prior intracranial hemorrhage (5.0%), allergy (2.4%), occupational risk (0.8%), pregnancy (0.2%), and other (12.6%). Among patients with reported contraindications, 30.3% were taking warfarin or dabigatran, as compared with 83.0% of those without reported contraindications. Besides "patient refusal/preference," being labeled as having frequent falls or being frail was associated with the lowest OAC use among patients with high stroke risk., Conclusions: Contraindications to OAC therapy among patients with AF are common but subjective. Many patients with reported contraindications were receiving OAC, suggesting that the perceived benefit outweighed the potential harm posed by the relative contraindication., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background: Dabigatran is a novel oral anticoagulant approved for thromboprophylaxis in atrial fibrillation. Adoption patterns of this new agent in community practice are unknown., Methods and Results: We studied patterns of dabigatran use among patients enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry between June 2010 and August 2011 and followed for 12 months. Among 9974 atrial fibrillation patients included, 1217 (12%) were treated with dabigatran during the study. Overall, patients receiving dabigatran were younger (median age 72 versus 75 years, P<0.0001), more likely to be white (92% versus 89%, P=0.005), more likely to have private insurance (33% versus 25%, P<0.0001), and less likely to have prior cardiovascular disease (4% versus 33%, P<0.0001). They had more new-onset atrial fibrillation (8.8% versus 4.1%, P<0.0001), lower CHADS2 scores (estimated risk based on the presence of congestive heart failure, hypertension, aged ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack; mean 2.0 versus 2.3, P<0.0001), and lower Anticoagulation and Risk Factors in Atrial Fibrillation scores (mean 2.4 versus 2.8, P<0.0001). More than half (n=14/25, 56%) of patients with severe kidney disease were not prescribed reduced dosing, whereas 10% (n=91/920) with preserved renal function received lower dosing. Among patients not on dabigatran at baseline, 8% had dabigatran initiated during follow-up. Patient education was significantly associated with switching from warfarin to dabigatran (adjusted odds ratio for postgraduate 1.73, P=0.007), whereas antiarrhythmic drug use significantly correlated with de novo adoption of dabigatran (adjusted odds ratio 2.4, P<0.0001)., Conclusions: Patients receiving dabigatran were younger and at a lower risk of stroke and bleeding. Patients appeared to drive switching from warfarin, whereas clinical characteristics influenced de novo start of dabigatran. These data suggest cautious early uptake of dabigatran, and more careful attention to dosing adjustments is warranted., Clinical Trial Registration Url: Clinicaltrials.gov. Unique identifier: NCT01165710.

Background: Patients with atrial fibrillation who are vitamin K antagonist (VKA)-naive may have a higher risk of thrombosis and/or bleeding than VKA-experienced patients., Methods and Results: Using data from ARISTOTLE, we assessed baseline characteristics and the treatment effect of apixaban versus warfarin in the VKA-naive and VKA-experienced cohorts. We compared rates of study drug discontinuation and time-in-therapeutic range. Overall, 7,800 (43%) were VKA naive, and 10,401 were VKA experienced. At baseline, both groups were similar with respect to age and congestive heart failure, hypertension, age, diabetes, stroke score (CHADS2). Fewer VKA-naive patients had a history of prior stroke (18% vs 21%) or prior bleeding (10% vs 22%) and were more often female (39% vs 33%). The effect of apixaban on the primary efficacy and safety outcomes was similar in VKA-naive (stroke/systemic embolism: hazard ratio [HR] 0.86, 95% CI 0.67-1.11 and major bleeding: HR 0.73, 95% CI 0.59-0.91) and VKA-experienced populations (stroke/systemic embolism: HR 0.73, 95% CI 0.57-0.95, P value for interaction = 0.39 and major bleeding: HR 0.66, 95% CI 0.55-0.80, P value for interaction = 0.50). Permanent study drug discontinuation was numerically less likely in patients receiving apixaban whether they were VKA naive (HR for discontinuation: 0.87, 95% CI 0.79-0.95) or VKA experienced (HR for discontinuation: 0.93, 95% CI 0.85-1.02). Among patients receiving warfarin, the mean/median times in therapeutic range were lower in the VKA-naive group (VKA-naive: 57.5/61.4, VKA-experienced: 66.0/69.1, P < .001)., Conclusion: The treatment effects of apixaban (vs warfarin) were not modified by VKA naivety. The rates of stroke/systemic embolism and major bleeding were numerically lower among the patients assigned to apixaban, irrespective of prior VKA use., (Copyright © 2013 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 often have cardiovascular risk factors or known comorbid disease, yet the use of evidence-based primary and secondary prevention cardiac therapy among atrial fibrillation outpatients is unknown., Methods: Using baseline data collected between June 2010 and August 2011 from 174 sites participating in ORBIT-AF, a US national registry of patients with atrial fibrillation coordinated from Durham, NC, we examined professional guideline-recommended evidence-based therapy use for cardiovascular comorbid conditions and risk factors. Multivariable logistic regression was used to identify factors associated with receipt of all indicated evidence-based therapy., Results: Among 10,096 enrolled patients, 93.5% were eligible for one or more evidence-based therapies. Among those eligible, 46.6% received all indicated therapies: 62.3% received an antiplatelet agent, 72.3% received a beta-blocker, 59.5% received an angiotensin-converting enzyme or angiotensin receptor blocker, 15.3% received an aldosterone antagonist, 65.7% received a statin, and 58.8% received an implantable cardioverter-defibrillator. A minority of patients with coronary artery disease, diabetes mellitus, heart failure, and peripheral vascular disease received all indicated therapies (25.1%, 43.2%, 42.5%, and 43.4%, respectively). A total of 52.4% of patients had controlled hypertension and 74.6% of patients with hyperlipidemia received a statin. Factors associated with nonreceipt of all indicated therapies included frailty, comorbid illness, geographic region, and antiarrhythmic drug therapy., Conclusions: The majority of eligible atrial fibrillation outpatients did not receive all guideline-recommended therapies for cardiovascular comorbid conditions and risk factors. This represents a potential opportunity to improve atrial fibrillation patients' quality of care and outcomes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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: In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced stroke and systemic embolism, major bleeding, and mortality. We evaluated treatment effects in relation to 2 predictions of time in therapeutic range (TTR)., Methods and Results: The trial randomized 18 201 patients with atrial fibrillation to apixaban 5 mg twice daily or warfarin for at least 12 months. For each patient, a center average TTR was estimated with the use of a linear mixed model on the basis of the real TTRs in its warfarin-treated patients, with a fixed effect for country and random effect for center. For each patient, an individual TTR was also predicted with the use of a linear mixed effects model including patient characteristics as well. Median center average TTR was 66% (interquartile limits, 61% and 71%). Rates of stroke or systemic embolism, major bleeding, and mortality were consistently lower with apixaban than with warfarin across center average TTR and individual TTR quartiles. In the lowest and highest center average TTR quartiles, hazard ratios for stroke or systemic embolism were 0.73 (95% confidence interval [CI], 0.53-1.00) and 0.88 (95% CI, 0.57-1.35) (Pinteraction=0.078), for mortality were 0.91 (95% CI, 0.74-1.13) and 0.91 (95% CI, 0.71-1.16) (Pinteraction=0.34), and for major bleeding were 0.50 (95% CI, 0.36-0.70) and 0.75 (95% CI, 0.58-0.97) (Pinteraction=0.095), respectively. Similar results were seen for quartiles of individual TTR., Conclusions: The benefits of apixaban compared with warfarin for stroke or systemic embolism, bleeding, and mortality appear similar across the range of centers' and patients' predicted quality of international normalized ratio control.

New oral anticoagulant drugs are emerging as alternatives to warfarin for the prevention of stroke in patients with non-valvular atrial fibrillation. Two agents are direct factor Xa inhibitors (rivaroxaban and apixaban), and the third is a direct thrombin inhibitor (dabigatran). They have been separately compared to warfarin in large randomised trials. Our objective was to indirectly compare the three agents to each other for major efficacy and safety outcomes. Studies were assessed for comparability and the odds ratios of selected outcomes for each anticoagulant versus one another were estimated indirectly. The three cohorts differed significantly in terms of CHADS(2) score and the number of individuals with a past history of stroke, transient ischemic attack or systemic embolism. The estimated odds ratio of stroke or systemic embolism was 1.35 for rivaroxaban vs dabigatran 150 mg (p=0.04), 0.97 for rivaroxaban versus dabigatran 110 mg (p=0.81), 1.22 for apixaban versus dabigatran 150 mg (p=0.18), 0.88 for apixaban versus dabigatran 110 mg (p=0.34) and 0.90 for apixaban versus rivaroxaban (p=0.43). The estimated odds ratio of major bleeding was 1.10 for rivaroxaban versus dabigatran 150 mg (p=0.36), 1.28 for rivaroxaban versus dabigatran 110 mg (p=0.02), 0.74 for apixaban versus dabigatran 150 mg (p=0.004), 0.87 for apixaban versus dabigatran 110 mg (p=0.17) and 0.68 for apixaban versus rivaroxaban (p<0.001). In conclusion, the available data indicate no significant difference in efficacy between dabigatran 150 mg and apixaban for the prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation. It appears however that apixaban is associated with less major bleeding than dabigatran 150 mg or rivaroxaban and that rivaroxaban is less effective than dabigatran 150 mg in preventing stroke or systemic embolism. Such an indirect comparison should be used only to generate hypotheses which need to be tested in a dedicated randomised trial comparing the three drugs directly.

Target-specific oral anticoagulants are now available for the prevention of stroke in patients with atrial fibrillation. These medications have many advantages, including fixed dosing, predictable anticoagulation without the need for monitoring, and few food or drug interactions. On the down side, their anticoagulant effects cannot be readily measured in clinical practice, and there are no known antidotes to reverse their anticoagulant effects. Clinical trials have shown superiority or noninferiority of these anticoagulants when compared with warfarin for reduction in incidence of stroke or systemic embolism, major bleeding, and mortality rates. Based on these findings, recent guidelines have supported the use of dabigatran compared with warfarin (other agents were not included in the guideline). Yet, there are concerns that these new agents may not be appropriate for all patients. Patients who are on warfarin and have stable and therapeutic anticoagulation may see no improvement in outcomes if changed to one of the new anticoagulants. Patients with decreased renal function may be at increased risk for bleeding if deterioration in renal function occurs. Management of bleeding events is complicated by the inability to reverse the new medications' anticoagulant effects. Medication noncompliance may result in more adverse outcomes due to the short half-life of these agents compared with warfarin. Prescribers need to be aware of these limitations as these medications are incorporated into clinical practice. Patients and clinicians need to understand the risk and benefits, and patients need to be engaged with their health care providers in decision making.

Safe and effective stroke prevention in atrial fibrillation (AF) is crucial as the number of patients with this condition continues to increase. Several novel oral anticoagulants are being developed as replacements for warfarin for this indication. Direct factor Xa inhibitors comprise the largest class of oral anticoagulants in development; the inhibition of factor Xa is recognized to be a promising target for therapeutic anticoagulation, partly because of its location in the coagulation cascade. Apixaban, betrixaban, edoxaban, and rivaroxaban are small-molecule, selective inhibitors that directly and reversibly bind to the active site of factor Xa. Their pharmacokinetic and pharmacodynamic profiles vary, which might allow patient-specific therapy. Several of these agents have been tested in clinical trials for various indications, including AF, with favorable results. In particular, apixaban and rivaroxaban have shown superiority and noninferiority, respectively, to warfarin in phase III clinical trials for stroke prevention in AF. These agents have also been shown to be safe in terms of bleeding risk. Despite these advantages, factor Xa inhibitors have several characteristics, such as potential interactions with other drugs (inhibitors of cytochrome P450 and P-glycoprotein) and the inability to reverse their anticoagulant effects, as well as concerns about poor patient compliance, which must be considered when initiating patients on a novel factor Xa inhibitor.