Outcomes registry for better informed treatment of atrial fibrillation: Rationale and design of ORBIT-AF

doi:10.1016/j.ahj.2011.07.001

American Heart Journal

Volume 162, Issue 4, October 2011, Pages 606-612.e1

https://doi.org/10.1016/j.ahj.2011.07.001 Get rights and content

Background

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with an increased risk of stroke, heart failure, and death. Data on contemporary treatment patterns and outcomes associated with AF in clinical practice are limited.

Methods/Design

The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation is a multicenter, prospective, ambulatory-based registry of incident and prevalent AF. The registry will be a nationwide collaboration of health care providers, including internists, primary care physicians, cardiologists, and electrophysiologists. Initial target enrollment is approximately 10,000 patients to be recruited from approximately 200 US outpatient practices. Enrolled patients will be observed for ≥2 years. A patient-reported outcomes substudy in ≥1,500 patients will provide serial quality-of-life assessments. The goal is to characterize treatment and outcomes of patients with AF, thereby promoting better quality of AF care and improved patient outcomes.

Conclusion

The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation will provide insights into “real-world” treatment including rate and rhythm control, stroke prevention, transitions to new therapies, and clinical and patient-centered outcomes among patients with AF in community practice settings (ClinicalTrials.gov NCT01165710).

Section snippets

Registry objectives

The ORBIT-AF registry has 5 main objectives: (1) characterize and describe a large representative AF population in the United States, including demographics, comorbidities, and risk profiles; (2) define current practice patterns for the treatment of patients with AF, particularly stroke prevention therapies; (3) identify how patterns of care and subsequent outcomes vary by risk stratification (ie, low risk vs high risk), including existing and novel risk prediction schema; (4) assess adherence

Initial enrolling site characteristics

Given the adaptive design of the registry, the composition of the enrolling sites is continuously monitored to ensure adequate provider, demographic, and geographic diversity and representativeness. Across the United States, 161 of 181 active sites enrolled the first 7,294 patients: 58 (36%) primary care and internal medicine clinics, 86 (53%) cardiology clinics, and 17 (11%) electrophysiology clinics. At the time of this writing, 181 sites were IRB approved and activated to enroll patients. As

Discussion

The Institute of Medicine has identified the management of AF as a top priority for comparative effectiveness research.²⁵ Atrial fibrillation increases the risk of stroke, cognitive impairment, and disability. Despite the presence of effective pharmacologic therapy for the prevention of stroke, anticoagulation prophylaxis in patients with AF is underused.²⁶ Because many patients with AF do not receive anticoagulation therapy or discontinue therapy within 1 year,²⁷ a key goal of ORBIT-AF will be

Conclusions

Although recent advances in the treatment of AF show promise for improved outcomes, no data exist to show how the results of these trials have influenced or will influence clinical practice. Prior studies have suggested that the application of evidence-based therapies remains suboptimal in patients with AF. The ORBIT-AF registry will examine current practice patterns, quality of care, and associated outcomes in the management of AF. These data will inform comparative effectiveness, comparative

Disclosures

The ORBIT-AF registry is sponsored by Ortho-McNeil Janssen Scientific Affairs, LLC, Raritan, NJ.

References (44)

V. Fuster et al.
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation—Executive summary: a report of the ACC/AHA Task Force on Practice Guidelines and the ESC Committee for Practice Guidelines
J Am Coll Cardiol
(2006)
P.S. Douglas et al.
Clinical effectiveness of coronary stents in elderly persons: results from 262,700 Medicare patients in the ACC–National Cardiovascular Data Registry
J Am Coll Cardiol
(2009)
H. Calkins et al.
HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures, and follow-up: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation
Heart Rhythm
(2007)
S. Schulman et al.
Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients
J Thromb Haemost
(2005)
R. Pisters et al.
A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey
Chest
(2010)
P.R. Kowey et al.
Warfarin and aspirin use in atrial fibrillation among practicing cardiologist (from the AFFECTS registry)
Am J Cardiol
(2010)
D.R. Holmes et al.
Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial
Lancet
(2009)
P. Dorian et al.
The impairment of health-related quality of life in patients with intermittent atrial fibrillation: implications for the assessment of investigational therapy
J Am Coll Cardiol
(2000)
P.A. Heidenreich et al.
Are registry hospitals different? A comparison of patients admitted to hospitals of a commercial heart failure registry with those from national and community cohorts
Am Heart J
(2006)
Y. Miyasaka et al.
Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence
Circulation
(2006)

L. Kilander et al.

Atrial fibrillation is an independent determinant of low cognitive function: A cross-sectional study in elderly men

Stroke

(1998)

T.J. Wang et al.

Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study

Circulation

(2003)

P.A. Wolf et al.

Atrial fibrillation as an independent risk factor for stroke: the Framingham Study

Stroke

(1991)

W.C. Lee et al.

Direct treatment cost of atrial fibrillation in the elderly American population: a Medicare perspective

J Med Econ

(2008)

S.J. Connolly et al.

Dabigatran versus warfarin in patients with atrial fibrillation

N Engl J Med

(2009)

S.H. Hohnloser et al.

Effect of dronedarone on cardiovascular events in atrial fibrillation

N Engl J Med

(2009)

Mahaffey KW. Rivaroxaban once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention...

M. Gheorghiade et al.

Reassessing treatment of acute heart failure syndromes: the ADHERE registry

Eur Heart J

(2005)

N.A. Estes et al.

ACC/AHA/Physician Consortium 2008 clinical performance measures for adults with nonvalvular atrial fibrillation or atrial flutter: a report of the ACC/AHA Task Force on Performance Measures and the Physician Consortium for Performance Improvement

Circulation

(2008)

L.S. Wann et al.

ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): a report of the ACC/AHA Task Force on Practice Guidelines

Circulation

(2011)

S.C. Chow et al.

Statistical consideration of adaptive methods in clinical development

J Biopharm Stat

(2005)

The ROCKET AF Study Investigators. Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation: rationale and design of the ROCKET AF study

Am Heart J

(2010)

Cited by (133)

Socioeconomic Status and Burden of Atrial Fibrillation Hospitalizations Among Black US Adults: A Fifteen Year Analysis
2023, Current Problems in Cardiology
Socioeconomic status (SES) may help delineate inequities in atrial fibrillation (AF) among Blacks versus non-blacks. We queried the National Inpatient Sample database from January 2004 to December 2018 to determine trends in AF hospitalizations and in-hospital mortality stratified by Black race and SES. Total admissions for AF in the US has increased by 12% from 1077 to 1202 per 1 million US adults. Among patients hospitalized with AF, the proportion of Black adults is increasing. In those of low SES, both Black and non-black patients have had increases in AF hospitalizations. In those of high SES, Black patients have had a modest increase while non-black patients have had a progressive decrease in rate of hospitalizations. Overall, in-hospital mortality rates improved in Blacks and non-blacks, regardless of SES. Joint associations of SES and race can further qualify disparities in AF care.
Residual stroke risk despite oral anticoagulation in patients with atrial fibrillation
2022, Heart Rhythm O2
Oral anticoagulation (OAC) reduces the risk of thromboembolic events in patients with atrial fibrillation (AF); however, thromboembolism (TE) still can occur despite OAC. Factors associated with residual risk for stroke, systemic embolism, or transient ischemic attack events despite OAC have not been well described.
The purpose of this study was to evaluate the residual risk of thromboembolic events in patients with AF despite OAC.
A total of 18,955 patients were analyzed in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF I and II) using multivariable Cox proportional hazard modeling. Mean age was 72 ± 10.7, and 42% were women. There were 451 outcome events.
The risk of TE despite OAC increased with CHA₂DS₂-VASc score: 0.76 (95% confidence interval [CI] 0.63–0.92) events per 100 patient-years for CHA₂DS₂-VASc score <4 vs 2.01 (95% CI 1.81–2.24) events per 100-patient years for CHA₂DS₂-VASc score >4. Factors associated with increased risk were previous stroke or transient ischemic attack (hazard ratio [HR] 2.87; 95% CI 2.30–3.59; P <.001), female sex (HR 1.52; 95% CI 1.24–1.86; P <.001), hypertension (HR 1.50; 95% CI 1.09–2.06; P = .01), and permanent AF (HR 1.47; 95% CI 1.12–1.94; P = .001). When transient ischemic attack was excluded, the results were similar, but permanent AF was no longer significantly associated with thromboembolic events.
Patients with AF have a residual risk of TE with increasing CHA₂DS₂-VASc score despite OAC. Key risk markers include previous stroke/transient ischemic attack, female sex, hypertension, and permanent AF.
Residual stroke risk in atrial fibrillation: Our patients must be our partners
2022, Heart Rhythm O2
Rhythm control versus rate control in patients with atrial fibrillation and heart failure across the left ventricular ejection fraction spectrum
2022, Hellenic Journal of Cardiology
Rhythm control and rate control are both employed commonly in patients with atrial fibrillation (AF) and heart failure (HF), but limited real-world data exist on them. We aimed to compare outcomes between these two strategies across the left ventricular ejection fraction (LVEF) spectrum.
This retrospective cohort study used data from the randomized MISOAC-AF trial, including from patients with AF and coexistent HF who were hospitalized and followed up after discharge. At baseline, the patients were classified into pharmaceutical (or electrical cardioversion) rhythm control strategy or rate control treatment (b-blocker, digoxin, calcium channel blockers) groups. The primary outcome was all-cause mortality. Kaplan-Meier curves and multivariable-adjusted Cox regression were utilized to compare the two strategies. Spline curve models were used to demonstrate the results across the LVEF stratified spectrum.
In total, 199 AF patients with HF were studied (mean age, 77 years). At discharge, 73 (36.7%) patients received rhythm control and 126 (63.3%) rate control treatment. After a median follow-up period of 31 months, 26 (35.6%) patients in the rhythm-control group died, as compared to 43 (33.3%) in the rate-control group (aHR: 1.29; 95% CI: 0.78-2.14; p = 0.31). The spline curves also revealed no difference in all-cause mortality favoring either strategy in any HF subtype across the nominally classified LVEF.
The use of a pharmacological rhythm-control strategy was not associated with a survival advantage compared to the rate control strategy in recently hospitalized patients with AF and comorbid HF. More randomized trials and large studies are needed in the future to explore these results in each subgroup of HF patients.
The importance of the design of observational studies in comparative effectiveness research: Lessons from the GARFIELD-AF and ORBIT-AF registries
2022, American Heart Journal
Randomized controlled trials (RCTs) are considered the gold standard for estimating the effectiveness of a treatment. However, in many instances they are impractical to conduct because of time limitations, cost restrictions, or ethical reasons. As a consequence, non-randomized observational studies have an important role in comparative effectiveness and safety research since they can address issues that would not be possible using conventional RCT methodology. Observational studies can be strategically designed to reduce the risk of potential sources of bias by emulating the design principles of an equivalent but ideal randomized trial – the target trial – that would answer the research question of interest.
In this article, we review some of the necessary components of observational studies required for valid causal inference within the framework of target trial emulation, so as to avoid common methodological pitfalls of study design. We discuss the assumptions of consistency, time-zero specification, exchangeability and positivity. To illustrate these concepts in a context where existing knowledge is well-established through clinical trials, we evaluate and compare the treatment effects of vitamin K antagonists (VKA) against no VKA (No VKA) on the treatment of atrial fibrillation from two real-world observational studies, namely the GARFIELD-AF and ORBIT-AF registries. Results are compared with those of published RCTs.
Rationale, design and basal characteristics of REGUEIFA study (Multicenter Registry of Atrial Fibrillation in Galicia)
2021, REC: CardioClinics
Evaluar el tratamiento y aplicación de las recomendaciones de las guías europeas del tratamiento de fibrilación auricular (FA), en una cohorte contemporánea de pacientes con FA.
REGUEIFA es un estudio observacional, prospectivo y multicéntrico de pacientes con diagnóstico primario o secundario de FA que residen en la comunidad autónoma de Galicia y son valorados por cardiólogos.
Se incluyeron 1.007 pacientes con una edad media de 67 años y 32% mujeres. Un 50% de pacientes tenía enfermedad cardiovascular. La amiodarona fue el fármaco antiarrítmico más utilizado (24,5%). El riesgo tromboembólico fue de 2,3 ± 1,5 en la escala CHA₂DS_2-VASc y el riesgo hemorrágico de 0,7 ± 0,7 en la escala HAS-BLED. Se prescribió tratamiento con anticoagulantes orales (ACO) en el 91,1%. Una mayor puntuación en la escala CHA₂DS_2-VASc, y la ablación de FA se identificaron como factores independientes asociados a ACO mientras que la forma paroxística se asoció a no anticoagulación. Se identificaron la edad y la insuficiencia renal como factores independientes de prescripción de antagonistas de la vitamina K mientras que la cardioversión eléctrica y la ablación de FA se asociaron de forma independiente a la prescripción de ACO de acción directa.
El estudio REGUEIFA proporciona información contemporánea del tratamiento cardiológico de pacientes con FA. La prescripción de ACO fue del 91,1%. Se describen los factores independientes asociados a la prescripción de ACO y de ACO de acción directa.
To assess the management and implementation of the European Society of Cardiology Guidelines on atrial fibrillation (AF), in a contemporary cohort of AF patients.
REGUEIFA is a prospective, multicenter and observational study of patients diagnosed with primary or secondary AF, dwelling in the region of Galicia and evaluated by cardiologists.
One thousand and seven patients have been recruited. Mean age was 67 ± 11 years and 32% were women. Fifty percent of patients have underlying cardiovascular disease. Amiodarone was the antiarrhythmic drug more often used (24,5%). The thromboembolic risk assessed by CHA₂DS_2-VASc score was 2.3 ± 1.5 and the bleeding risk assessed by HASBLED score was 0.7 ± 0.7. Oral anticoagulant therapy (OAC) was prescribed in 90.1%. CHA₂DS_2-VASc score, hypertension and AF ablation were independent predictor factors of OAC and paroxysmal AF was associated with no anticoagulation. Age and renal insufficiency, were independent predictor factors of vitamin K antagonists prescription whereas electrical cardioversion and AF ablation were independent predictor factors of direct oral anticoagulation therapy prescription.
REGUEIFA registry provides contemporary information on AF management by cardiologists. Prescription of OAC was 91,1%. Independent predictor factors associated with OAC and direct oral anticoagulation prescription were described.

View all citing articles on Scopus

: Jeanne E. Poole, MD served as guest editor for this article.

ⁱ: On behalf of the ORBIT-AF Steering Committee and Investigators.

View full text

Trial DesignOutcomes registry for better informed treatment of atrial fibrillation: Rationale and design of ORBIT-AF

Background

Methods/Design

Conclusion

Section snippets

Registry objectives

Initial enrolling site characteristics

Discussion

Conclusions

Disclosures

J Am Coll Cardiol

J Am Coll Cardiol

Heart Rhythm

J Thromb Haemost

Chest

Am J Cardiol

Lancet

J Am Coll Cardiol

Am Heart J

Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence

Circulation

Atrial fibrillation is an independent determinant of low cognitive function: A cross-sectional study in elderly men

Stroke

Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study

Circulation

Atrial fibrillation as an independent risk factor for stroke: the Framingham Study

Stroke

Direct treatment cost of atrial fibrillation in the elderly American population: a Medicare perspective

J Med Econ

Dabigatran versus warfarin in patients with atrial fibrillation

N Engl J Med

Effect of dronedarone on cardiovascular events in atrial fibrillation

N Engl J Med

Reassessing treatment of acute heart failure syndromes: the ADHERE registry

Eur Heart J

ACC/AHA/Physician Consortium 2008 clinical performance measures for adults with nonvalvular atrial fibrillation or atrial flutter: a report of the ACC/AHA Task Force on Performance Measures and the Physician Consortium for Performance Improvement

Circulation

ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): a report of the ACC/AHA Task Force on Practice Guidelines

Circulation

Statistical consideration of adaptive methods in clinical development

J Biopharm Stat

The ROCKET AF Study Investigators. Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation: rationale and design of the ROCKET AF study

Am Heart J

Trial Design
Outcomes registry for better informed treatment of atrial fibrillation: Rationale and design of ORBIT-AF