Outcomes Registry For Better Informed Treatment Of Atrial Fibrillation Research Articles

Predictors of intracranial hemorrhage in patients with atrial fibrillation treated with oral anticoagulants: Insights from the GARFIELD-AF and ORBIT-AF registries.

An unmet need exists to reliably predict the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs). An externally validated model improves ICH risk stratification. Independent factors associated with ICH were identified by Cox proportional hazard modeling, using pooled data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) and ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registries. A predictive model was developed and validated by bootstrap sampling and by independent data from the Danish National Patient Register. In the combined training data set, 284 of 53 878 anticoagulated patients had ICH over a 2-year period (0.31 per 100 person-years; 95% confidence interval [CI]: 0.28-0.35). Independent predictors of ICH included: older age, prior stroke or transient ischemic attack, concomitant antiplatelet (AP) use, and moderate-to-severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) were associated with a significantly higher risk of ICH compared with non-VKA oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25-2.08; p = .0002). The ability of the model to discriminate individuals in the training set with and without ICH was fair (optimism-corrected C-statistic: 0.68; 95% CI: 0.65-0.71) and outperformed three previously published methods. Calibration between predicted and observed ICH probabilities was good in both training and validation data sets. Age, prior ischemic events, concomitant AP therapy, and CKD were important risk factors for ICH in anticoagulated AF patients. Moreover, ICH was more frequent in patients receiving VKA compared to NOAC. The new validated model is a step toward mitigating this potentially lethal complication.

Machine learning does not improve upon traditional regression in predicting outcomes in atrial fibrillation: an analysis of the ORBIT-AF and GARFIELD-AF registries.

Prediction models for outcomes in atrial fibrillation (AF) are used to guide treatment. While regression models have been the analytic standard for prediction modelling, machine learning (ML) has been promoted as a potentially superior methodology. We compared the performance of ML and regression models in predicting outcomes in AF patients. The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) and Global Anticoagulant Registry in the FIELD (GARFIELD-AF) are population-based registries that include 74792 AF patients. Models were generated from potential predictors using stepwise logistic regression (STEP), random forests (RF), gradient boosting (GB), and two neural networks (NNs). Discriminatory power was highest for death [STEP area under the curve (AUC) = 0.80 in ORBIT-AF, 0.75 in GARFIELD-AF] and lowest for stroke in all models (STEP AUC = 0.67 in ORBIT-AF, 0.66 in GARFIELD-AF). The discriminatory power of the ML models was similar or lower than the STEP models for most outcomes. The GB model had a higher AUC than STEP for death in GARFIELD-AF (0.76 vs. 0.75), but only nominally, and both performed similarly in ORBIT-AF. The multilayer NN had the lowest discriminatory power for all outcomes. The calibration of the STEP modelswere more aligned with the observed events for all outcomes. In the cross-registry models, the discriminatory power of the ML models was similar or lower than the STEP for most cases. When developed from two large, community-based AF registries, ML techniques did not improve prediction modelling of death, major bleeding, or stroke.

Guideline-directed therapies for comorbidities and clinical outcomes among individuals with atrial fibrillation

Comorbidities are common in patients with atrial fibrillation (AF) and affect prognosis, yet are often undertreated. However, contemporary rates of use of guideline-directed therapies (GDT) for non-AF comorbidities and their association with outcomes are not well described. We used the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF) to test the association between GDT for non-AF comorbidities and major adverse cardiac or neurovascular events (MACNE; cardiovascular death, myocardial infarction, stroke/thromboembolism, or new-onset heart failure), all-cause mortality, new-onset heart failure, and AF progression. Adjustment was performed using Cox proportional hazards models and logistic regression. Only 6,782 (33%) of the 20,434 patients eligible for 1 or more GDT for non-AF comorbidities received all indicated therapies. Use of all comorbidity-specific GDT was highest for patients with hyperlipidemia (75.6%) and lowest for those with diabetes mellitus (43.1%). Use of "all eligible" GDT was associated with a nonsignificant trend toward lower rates of MACNE (HR 0.90 [0.79-1.02]) and all-cause mortality (HR 0.90 [0.80-1.01]). Use of GDT for heart failure was associated with a lower risk of all-cause mortality (HR 0.77 [0.67-0.89]), and treatment of obstructive sleep apnea was associated with a lower risk of AF progression (OR 0.75 [0.62-0.90]). In AF patients, there is underuse of GDT for non-AF comorbidities. The association between GDT use and outcomes was strongest in heart failure and obstructive sleep apnea patients where use of GDT was associated with lower mortality and less AF progression.

Association Between Warfarin Control Metrics and Atrial Fibrillation Outcomes in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation

Bleeding and thrombotic events (eg, stroke and systemic embolism) are common in patients with atrial fibrillation (AF) taking warfarin sodium despite a well-established therapeutic range. To evaluate whether history of therapeutic warfarin control in patients with AF is independently associated with subsequent bleeding or thrombotic events. In this multicenter cohort study of 176 primary care, cardiology, and electrophysiology clinics in the United States, data were obtained during 51 830 visits among 10 137 patients with AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry; 5545 patients treated with warfarin were included in the bleeding analysis, and 5635 patients were included in the thrombotic event analysis. Patient follow-up was performed from June 29, 2010, to November 30, 2014. Data analysis was performed from August 4, 2016, to February 15, 2019. Multiple measures of warfarin control within the preceding 6 months were analyzed: time in therapeutic range of 2.0 to 3.0, most recent international normalized ratio (INR), percentage of time that a patient had interpolated INR values less than 2.0 or greater than 3.0, INR variance, INR range, and percentage of INR values in therapeutic range. Association of INR measures, alone or in combination, with clinical factors and risk for thrombotic events and bleeding during the subsequent 6 months was assessed post hoc using logistic regression models. A total of 5545 patients (mean [SD] age, 74.5 [9.8] years; 3184 [57.4%] male) with AF were included in the major bleeding analysis and 5635 patients (mean [SD] age, 74.5 [9.8] years; 3236 [57.4%] male) in the thrombotic event analysis. During a median follow-up of 1.5 years (interquartile range, 1.0-2.5 years), there were 339 major bleeds (6.1%) and 51 strokes (0.9%). Multiple metrics of warfarin control were individually associated with subsequent bleeding. After adjustment for clinical bleeding risk, 3 measures-time in therapeutic range (per 1-SD increase ≤55: adjusted odds ratio [aOR], 1.16; 95% CI, 1.02-1.32), variation in INR values (aOR, 1.32; 95% CI, 1.19-1.47), and maximum INR (aOR, 1.20; 95% CI, 1.10-1.31)-remained associated with bleeding risk. Adding INR variance to a clinical risk model slightly increased the C statistic from 0.68 to 0.69 and had a net reclassification improvement index of 0.028 (95% CI, -0.029 to 0.067). No INR measures were associated with subsequent stroke risk. Three metrics of prior warfarin control were associated with bleeding risk but only marginally more so than traditional clinical factors. This study did not identify any measures of INR control that were significantly associated with stroke risk.

Defining Clinically Important Difference in the Atrial Fibrillation Effect on Quality-of-Life Score

Background The Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire has recently been validated to measure the impact of atrial fibrillation on quality of life, but a clinically important difference in AFEQT score has not been well defined. Methods and Results To determine the clinically important difference in overall AFEQT (score range= 0 [worst] to 100 [best]) and selected subscales, we analyzed data in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry, a United States-based outpatient atrial fibrillation registry. AFEQT was assessed at baseline and 1 year in a subset of 1347 ORBIT-AF patients from 80 US sites participating in ORBIT-AF from June 2010 to August 2011. The mean change method was used to relate changes in 1-year AFEQT scores to clinically important changes in the physician assessment of European Heart Rhythm Association functional status (1 class improvement and separately 1 class deterioration). Clinically important differences and 95% CI corresponding to either a 1 European Heart Rhythm Association class improvement or deterioration were 5.4 (3.6-7.2) and -4.2 (-6.9 to -1.5) AFEQT points, respectively. Similarly, clinically important difference values were seen for a 1 European Heart Rhythm Association class improvement for the AFEQT subscales Activities of Daily Living and Symptoms: 5.1 (2.5-7.6) and 7.1 (5.3-9.0) AFEQT points, respectively. Conclusions Based on the anchor of 1 European Heart Rhythm Association class change, changes in AFEQT score of + or -5 points are clinically important changes in patients' health. Clinical Trial Registration URL: https://clinicaltrials.gov . Unique identifier: NCT01165710.

Stroke Risk and Treatment in Patients with Atrial Fibrillation and Low CHA2DS2-VASc Scores: Findings From the ORBIT-AF I and II Registries.

BackgroundCurrent American College of Cardiology/American Heart Association guidelines suggest that for patients with atrial fibrillation who are at low risk for stroke (CHA2DS2VASc=1) (or women with CHA2DS2VASc=2) a variety of treatment strategies may be considered. However, in clinical practice, patterns of treatment in these “low‐risk” patients are not well described. The objective of this analysis is to define thromboembolic event rates and to describe treatment patterns in patients with low‐risk CHA2DS2VASc scores.Methods and ResultsWe compared characteristics, treatment strategies, and outcomes among patients with a CHA2DS2VASc=0, CHA2DS2VASc=1, females with a CHA2DS2VASc=2, and CHA2DS2VASc ≥2 in ORBIT‐AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) I & II. Compared with CHA2DS2VASc ≥2 patients (84.2%), those with a CHA2DS2VASc=0 (60.3%), 1 (69.9%), and females with a CHA2DS2VASc score=2 (72.4%) were significantly less often treated with oral anticoagulation (P<0.0001). Stroke rates were low overall and ranged from 0 per 100 patient‐years in those with CHA2DS2VASc=0, 0.8 (95% confidence interval [CI] [0.5–1.2]) in those with CHA2DS2VASc=1, 0.8 (95% CI [0.4–1.6]) in females with a CHA2DS2VASc score=2, and 1.7 (95% CI [1.6–1.9]) in CHA2DS2VASc ≥2. All‐cause mortality (per 100 patient‐years) was highest in females with a CHA2DS2VASc score=2 (1.4) (95% CI [0.8–2.3]), compared with patients with a CHA2DS2VASc=0 (0.2) (95% CI [0.1–1.0]), and CHA2DS2VASc=1 (1.0) (95% CI [0.7–1.4]), but lower than patients with a CHA2DS2VASc ≥2 (5.7) (95% CI [5.4–6.0]).ConclusionThe majority of CHA2DS2VASc=0‐1 patients are treated with oral anticoagulation. In addition, the absolute risks of death and stroke/transient ischemic attack were low among both male and females CHA2DS2VASc=0‐1 as well as among females with a CHA2DS2VASc score=2.Clinical Trial RegistrationURL:http://www.clinicaltrials.gov. Unique identifier: NCT01701817.

Incremental prognostic value of renal function for stroke prediction in atrial fibrillation

BackgroundRenal 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. MethodsWe 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). ResultsAmong 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 CHADS2 or CHA2DS2-VASc). Discrimination for predicting stroke (C-index; 95% CI) was similar for R2CHADS2 (0.65; 0.61–0.69), CHADS2 (0.65; 0.61–0.69), and CHA2DS2-VASc (0.66; 0.62–0.70). Conclusions and relevanceIn 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.

Mineralocorticoid Receptor Antagonism in Patients With Atrial Fibrillation: Findings From the ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) Registry.

BackgroundMineralocorticoid receptor antagonist (MRA) therapy may be beneficial to patients with atrial fibrillation (AF), but little is known about their use in patients with AF and subsequent outcomes.Methods and ResultsIn order to better understand MRA use and subsequent outcomes, we performed a retrospective cohort study of the contemporary ORBIT‐AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry. AF progression and cardiovascular outcomes were compared using propensity‐matched Cox proportional hazards modeling according to MRA use at baseline and new MRA use at follow‐up versus patients with no MRA use. Among 7012 patients with nonpermanent AF, 320 patients were taking MRA at enrollment, and 416 patients initiated MRA use during follow‐up. The mean patient age was 72.5 years, 56.3% were men, and 70.4% had paroxysmal AF. Among all patients taking MRAs, 434 (59.0%) had heart failure, 655 (89.0%) had hypertension, and 380 (51.6%) had both. After adjustment, new MRA use was not associated with reduced AF progression (hazard ratio, 1.18; 95% confidence interval, 0.88–1.58; P=0.27) but showed a trend towards lower risk of stroke, transient ischemic attack, or systemic embolism (hazard ratio, 0.17; 95% confidence interval, 0.02–1.23; P=0.08). Results were similar for a comparison of new MRA users and baseline MRA users compared with nonusers.ConclusionsIn community‐based outpatients with AF, the majority of MRA use was for heart failure and hypertension. MRA use also trended towards lower adjusted stroke risk. Future studies should test the hypothesis that MRA use may decrease the risk of stroke in patients with AF.

Association of of Atrial Fibrillation Clinical Phenotypes With Treatment Patterns and Outcomes

Atrial fibrillation (AF) is usually classified on the basis of the disease subtype. However, this characterization does not capture the full heterogeneity of AF, and a data-driven cluster analysis reveals different possible classifications of patients. To characterize patients with AF based on a cluster analysis and to evaluate the association between these phenotypes, treatment, and clinical outcomes. This cluster analysis used data from an observational cohort that included 9749 patients with AF who had been admitted to 174 US sites participating in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry. Data analysis was completed from January 2017 to October 2017. Patients with diagnosed AF who were included in the registry. Composite of major adverse cardiovascular or neurological events and major bleeding, as defined by the International Society of Thrombosis and Hemostasis criteria. Of 9749 total patients, 4150 (42.6%) were female; 8719 (89.4%) were white and 477 (4.9%) were African American. A cluster analysis was performed using 60 baseline clinical characteristics, and it classified patients with AF into 4 statistically driven clusters: (1) those with considerably lower rates of risk factors and comorbidities than all other clusters (n = 4673); (2) those with AF at younger ages and/or with comorbid behavioral disorders (n = 963); (3) those with AF who had similarities to patients with tachycardia-brachycardia and had device implantation owing to sinus node dysfunction (n = 1651); and (4) those with AF and prior coronary artery disease, myocardial infarction, and/or atherosclerotic comorbidities (n = 2462). Conventional classifications, such as AF subtype and left atrial size, did not drive cluster formation. Compared with the low comorbidity AF cluster, adjusted risks of major adverse cardiovascular or neurological events were significantly higher in the other 3 clusters (behavioral comorbidity cluster: hazard ratio [HR], 1.49; 95% CI, 1.10-2.00; device implantation cluster: HR, 1.39; 95% CI, 1.15-1.68; and atherosclerotic comorbidity cluster: HR, 1.59; 95% CI, 1.31-1.92). For major bleeding, adjusted risks were higher in the behavioral disorder comorbidity cluster (HR, 1.35; 95% CI, 1.05-1.73), those with device implantation (HR, 1.24; 95% CI, 1.05-1.47), and those with atherosclerotic comorbidities (HR, 1.13; 95% CI, 0.96-1.33) compared with the low comorbidity cluster. The same clusters were identified in an external validation in the ORBIT AF II registry. Cluster analysis identified 4 clinically relevant phenotypes of AF that each have distinct associations with clinical outcomes, underscoring the heterogeneity of AF and importance of comorbidities and substrates.

In This Issue: November

In This Issue: November

Treatment of Atrial Fibrillation and Concordance With the American Heart Association/American College of Cardiology/Heart Rhythm Society Guidelines: Findings From ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation).

It is unclear how frequently patients with atrial fibrillation receive guideline-concordant (GC) care and whether guideline concordance is associated with improved outcomes. 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 CHA2DS2-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. 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.

Care Patterns and Outcomes in Atrial Fibrillation Patients With and Without Diabetes: ORBIT-AF Registry

BackgroundDiabetes is a well-established risk factor for thromboembolism in patients with atrial fibrillation (AF), but less is known about how diabetes influences outcomes among AF patients. ObjectivesThis study assessed whether symptoms, health status, care, and outcomes differ between AF patients with and without diabetes. MethodsThe cohort study included 9,749 patients from the ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry, a prospective, nationwide, outpatient registry of patients with incident and prevalent AF. Outcomes included symptoms, health status, and AF treatment, as well as 2-year risk of death, hospitalization, thromboembolic events, heart failure (HF), and AF progression. ResultsPatients with diabetes (29.5%) were younger, more likely to have hypertension, chronic kidney disease, HF, coronary heart disease, and stroke. Compared to patients without diabetes, patients with diabetes also had a lower Atrial Fibrillation Effects on Quality of Life score of 80 (interquartile range [IQR]: 62.5 to 92.6) versus 82.4 (IQR: 67.6 to 93.5; p = 0.025) and were more likely to receive anticoagulation (p < 0.001). Diabetes was associated with higher mortality risk, including overall (adjusted hazard ratio [aHR]: 1.63; 95% confidence interval [CI]: 1.04 to 2.56, for age <70 years vs. aHR: 1.25; 95% CI: 1.09 to 1.44, for age ≥70 years) and cardiovascular (CV) mortality (aHR: 2.20; 95% CI: 1.22 to 3.98, for age <70 years vs. 1.24; 95% CI: 1.02 to 1.51 for age ≥70 years). Diabetes conferred a higher risk of non-CV death, sudden cardiac death, hospitalization, CV hospitalization, and non-CV and nonbleeding-related hospitalization, but no increase in risks of thromboembolic events, bleeding-related hospitalization, new-onset HF, and AF progression. ConclusionsAmong AF patients, diabetes was associated with worse AF symptoms and lower quality of life, and increased risk of death and hospitalizations, but not thromboembolic or bleeding events.

How well does physician risk assessment predict stroke and bleeding in atrial fibrillation? Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF)

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. 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, CHADS2 and CHA2DS2-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. 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 CHADS2 (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 (Padjusted>.05 for all physician assessments vs Padjusted<.05 for empirical scores). 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.

ADHERENCE TO GUIDELINE RECOMMENDATIONS IN ATRIAL FIBRILLATION: FINDINGS FROM ORBIT-AF

Although clinical practice guidelines are commonly used to guide patient care in atrial fibrillation (AF), data regarding adherence to guideline recommendations are limited. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), we assessed adherence to a

Family history of atrial fibrillation is associated with earlier-onset and more symptomatic atrial fibrillation: Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry

We addressed whether patients with a family history of atrial fibrillation (AF) were diagnosed as having AF earlier in life, were more symptomatic, and had worse outcomes compared with those without a family history of AF. Using the ORBIT-AF, we compared symptoms and disease characteristics in those with and without a family history of AF. A family history of AF was defined as AF in a first-degree family member and obtained by patient self-reporting. Multivariable Cox proportional hazard analyses were performed to compare the incidence of cardiovascular outcomes, AF progression, all-cause hospitalization, and all-cause death. Among 9,999 patients with AF from 176 US outpatient clinics, 1,481 (14.8%) had a family history of AF. Relative to those without, those with a family history of AF developed AF 5 years earlier on average (median age 65 vs 70 years, P < .01), with less comorbidity, and had more severe AF-related symptoms. No differences were found between the 2 groups in the risk of AF progression (adjusted hazard ratio [HR] 0.98, 95% CI 0.85-1.14), stroke, non-central nervous system embolism, or transient ischemic attack (adjusted HR 0.95, 95% CI 0.67-1.34), all-cause hospitalization (adjusted HR 1.03, 95% CI 0.94-1.12), and all-cause death (adjusted HR 1.05, 95% CI 0.86-1.27). Patients with a family history of AF developed AF at a younger age, had less comorbidity, and were more symptomatic. Once AF developed, no significantly increased risks of AF progression and thromboembolism were associated with a family history of AF compared with no family history.

Use and Outcomes Associated With Bridging During Anticoagulation Interruptions in Patients With Atrial Fibrillation: Findings From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF)

Use and Outcomes Associated With Bridging During Anticoagulation Interruptions in Patients With Atrial Fibrillation: Findings From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF)

Association of Body Mass Index WithCareand Outcomes in Patients WithAtrialFibrillation: Results From the ORBIT-AF Registry.

This study sought to determine the association between body mass index (BMI) and clinical outcomes among patients with prevalent atrial fibrillation (AF). Higher BMI is an independent risk factor for incident AF. However, its impact on management strategies and clinical outcomes among patients with prevalent AF is unclear. Patients with AF enrolled in the ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry from June 2010 through August 2011 were stratified into BMI-based categories as normal weight, overweight, class I obese, class II obese, and class III obese. Unadjusted and adjusted Cox frailty models were constructed to assess the association of BMI with clinical outcomes over a 2-year follow-up. We evaluated 9,606 patients with AF (42% women; 78% overweight/obese) from 174 ORBIT participating practices in the United States. Higher BMI patients were younger and had a greater prevalence of diabetes, hypertension, and obstructive sleep apnea (OSA). Use of anticoagulation and rhythm control strategies was significantly greater among higher BMI patients. Rates for all-cause mortality and thromboembolic events decreased in a near linear fashion across increasing BMI categories (p< 0.001). After multivariable adjustment, higher BMI was associated with lower risk for all-cause mortality with lowest risk among class I obese patients (hazard ratio [HR]: 0.65; 95% CI: 0.54 to 0.78); reference: normal weight). For every 5-kg/m2 increase in BMI, the odds of risk-adjusted mortality were 7% lower. Incontrast, BMI was not associated with adjusted risk for thromboembolic events and AF progression. Although AF patients with higher BMI were significantly younger, higher BMI in AF patients was associated with similar or better clinical outcomes.

Abstract 9992: Rhythm Control Versus Rate Control and Clinical Outcomes in Patients With Atrial Fibrillation: Results From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF)

Introduction: Randomized trials have not demonstrated significant differences in stroke, heart failure or mortality between rhythm and rate control strategies for management of atrial fibrillation (AF). The comparative outcomes in contemporary clinical practice are not well described. The objective of this study was to evaluate outcomes in clinical practice with rhythm control versus rate control strategy. Methods: Patients managed with a rhythm control strategy targeting maintenance of sinus rhythm were retrospectively compared with a strategy of rate control alone in a AF registry across various US practice settings. Unadjusted and adjusted (inverse-propensity weighted) outcomes were estimated. Results: The overall study population (n=6988) had a median age of 74 (25th, 75th percentile 65, 81) years, 56% were males, 77% had first detected or paroxysmal AF and 89% had CHA2DS2-VASc score ≥2. In unadjusted analyses, rhythm control was associated with lower all-cause death, cardiovascular death, first stroke/non-central nervous system systemic embolization/transient ischemic attack, or first major bleeding event (all p&lt;0.05); however, rhythm control was associated with more cardiovascular hospitalizations (HR 1.24, 95% CI 1.10-1.39, p=0.0003; Figure). Conclusion: Among patients with AF in clinical practice, rhythm control was not superior to rate control strategy for outcomes of stroke, heart failure, or mortality, but was associated with more cardiovascular hospitalizations.

The ORBIT bleeding score: a simple bedside score to assess bleeding risk in atrial fibrillation

BackgroundTherapeutic decisions in atrial fibrillation (AF) are often influenced by assessment of bleeding risk. However, existing bleeding risk scores have limitations.ObjectivesWe 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.MethodsWe 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).ResultsAmong 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.ConclusionsThe 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.

Increased Heart Rate Is Associated With Higher Mortality in Patients With Atrial Fibrillation (AF): Results From the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF).

BackgroundMost patients with atrial fibrillation (AF) require rate control; however, the optimal target heart rate remains under debate. We aimed to assess rate control and subsequent outcomes among patients with permanent AF.Methods and ResultsWe studied 2812 US outpatients with permanent AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation. Resting heart rate was measured longitudinally and used as a time-dependent covariate in multivariable Cox models of all-cause and cause-specific mortality during a median follow-up of 24 months. At baseline, 7.4% (n=207) had resting heart rate <60 beats per minute (bpm), 62% (n=1755) 60 to 79 bpm, 29% (n=817) 80 to 109 bpm, and 1.2% (n=33) ≥110 bpm. Groups did not differ by age, previous cerebrovascular disease, heart failure status, CHA2DS2-VASc scores, renal function, or left ventricular function. There were significant differences in race (P=0.001), sinus node dysfunction (P=0.004), and treatment with calcium-channel blockers (P=0.006) and anticoagulation (P=0.009). In analyses of continuous heart rates, lower heart rate ≤65 bpm was associated with higher all-cause mortality (adjusted hazard ratio [HR], 1.15 per 5-bpm decrease; 95% CI, 1.01 to 1.32; P=0.04). Similarly, increasing heart rate >65 bpm was associated with higher all-cause mortality (adjusted HR, 1.10 per 5-bpm increase; 95% CI, 1.05 to 1.15; P<0.0001). This relationship was consistent across endpoints and in a broader sensitivity analysis of permanent and nonpermanent AF patients.ConclusionsAmong patients with permanent AF, there is a J-shaped relationship between heart rate and mortality. These data support current guideline recommendations, and clinical trials are warranted to determine optimal rate control.Clinical Trial RegistrationURL: http://clinicaltrials.gov/. Unique identifier: NCT01165710.