1. Symptoms based on EHRA score
Comparing Incidence of Stroke and non-CNS Embolism in Patients with Symptomatic and Asymptomatic Atrial Fibrillation: Insights from the ORBIT-AF Registry
Munveer Thind1, DaJuanicia Holmes2, Marwan Badri3, Karen Pieper2, Amitoj Singh4, Rosalia Blanco2, Gregg C. Fonarow5, Bernard J. Gersh6, Kenneth W. Mahaffey7, Eric D. Peterson2, Jonathan P. Piccini2, Peter R. Kowey3 on behalf of the ORBIT-AF patients and investigators.
1Lankenau Medical Center, Wynnewood, PA, Department of Internal Medicine; 2Duke Clinical Research Institute, Durham, NC; 3Lankenau Medical Center, Wynnewood, PA, Division of Cardiology; 4Brigham and Women’s Hospital, Boston, MA, Department of Noninvasive Cardiac Imaging; 5University of California, Los Angeles, LA, CA, Division of Cardiology; 6Mayo Clinic College of Medicine, Rochester, MN, Division of Cardiology; 7Stanford Center for Clinical Research (SCCR), Stanford University, Stanford, CA, Department of Medicine
BACKGROUND
RESULTS
Baseline Characteristics in Asymptomatic and Symptomatic Patients with Atrial Fibrillation:
Outcomes in Asymptomatic and Symptomatic Patients with Atrial Fibrillation:
Symptoms based on EHRA score
Overall
N=9319
EHRA = 1 N=3582 (38%)
EHRA ≥2 N=5737 (62%)
P value
Demographics/Vitals
Age
75.0 (67.0,82.0)
76.0 (68.0,82.0)
74.0 (66.0,81.0)
<0.0001
Female
3944 (42.3)
1269 (35.4)
2675 (46.6)
Race/ethnicity
White
Black
Hispanic
Other
0.0002
8344 (89.5)
3203 (89.4)
5141 (89.6)
450 (4.8)
147 (4.1)
303 (5.3)
377 (4.0)
179 (5.0)
198 (3.5)
133 (1.4)
48 (1.3)
85 (1.5)
Payor/Insurance
Medicare/Medicaid
Private
0.02
6536 (70.1)
2572 (71.8)
3964 (69.1)
2351 (25.2)
854 (23.8)
1497 (26.1)
431 (4.6)
156 (4.4)
275 (4.8)
BMI
29.2 (25.4,34.1)
29.1 (25.7,33.6)
29.3 (25.2,34.5)
0.43
Heart rate
70.0 (63.0,80.0)
70.0 (62.0,79.0)
Systolic BP
126.0 (116.0,138.0)
126.0 (118.0,138.0)
124.0 (115.0,138.0)
0.005
Diastolic BP
72.0 (66.0,80.0)
72.0 (67.0,80.0)
0.11
Medical history
Hypertension
7765 (83.3)
3003 (83.8)
4762 (83.0)
0.30
Hyperlipidemia
6717 (72.1)
2668 (74.5)
4049 (70.6)
Diabetes
2747 (29.5)
1061 (29.6)
1686 (29.4)
0.81
Chronic kidney disease (CKD)
3180 (34.1)
1186 (33.1)
1994 (34.8)
0.17
CKD on dialysis
117 (1.3)
44 (1.2)
73 (1.3)
0.85
Anemia
1671 (17.9)
631 (17.6)
1040 (18.1)
0.53
Smoking status
Non-smoker
Recent/former smoker
Current smoker
0.16
4812 (51.6)
1832 (51.1)
2980 (51.9)
3971 (42.6)
1560 (43.6)
2411 (42.0)
535 (5.7)
189 (5.3)
346 (6.0)
Congestive heart failure (CHF)
2969 (31.9)
1011 (28.2)
1958 (34.1)
Implanted device
2509 (26.9)
899 (25.1)
1610 (28.1)
0.002
Coronary artery disease
3333 (35.8)
1292 (36.1)
2041 (35.6)
0.63
Stroke/TIA
1383 (14.8)
519 (14.5)
864 (15.1)
0.45
Type of AF
New onset
Paroxysmal
Persistent/Permanent
426 (4.6)
120 (3.4)
306 (5.3)
4777 (51.3)
1643 (45.9)
3134 (54.6)
4116 (44.2)
1819 (50.8)
2297 (40.0)
Management strategy
Rate control
Rhythm control
6309 (67.7)
2640 (73.7)
3669 (64.0)
2985 (32.0)
931 (26.0)
2054 (35.8)
Medications
Oral anticoagulants
7054 (75.7)
2762 (77.1)
4292 (74.8)
0.01
Anti-platelets
4429 (47.5)
1662 (46.4)
2767 (48.2)
0.08
Anti-arrhythmics
2702 (29.0)
802 (22.4)
1900 (33.1)
Stroke risk scores
CHADS2 score
CHA2DS2VASc score
2.0 (1.0,3.0)
0.9
4.0 (3.0,5.0)
0.18
Bleeding risk scores
Atria score
ORBIT score
3.0 (1.0,4.0)
0.05
2.0 (1.0,4.0)
0.54
1. At baseline, symptomatic AF patients were more likely to be female, have CHF, have paroxysmal AF, and be prescribed anti-arrhythmics
Atrial fibrillation (AF) can be symptomatic or asymptomatic
Asymptomatic AF is being increasingly diagnosed via interrogation of implanted devices1 and screening with insertable cardiac monitors2-4
Management of asymptomatic AF remains controversial as the associated adverse events have not been well described
This study was thus designed to examine the incidence of major adverse outcomes in patients with asymptomatic versus symptomatic AF
METHODS
Data Source:
ORBIT-AF is an observational, prospective registry of patients with incident or prevalent AF from a variety of outpatient practices across 176 sites throughout the United States
Population:
After exclusions (no documented symptoms score, mechanical heart valve, moderate/severe mitral stenosis, missing follow-up data) the study population included 9,319 patients across 174 sites
Definitions and Outcomes:
Asymptomatic patients were defined by having an EHRA symptom score of 1, or by the absence of symptoms based on the itemized symptom checklist filled in by patients
Patients were followed at 6 month intervals for a minimum of 2 years and up to a maximum of 3 years
Outcomes
First stroke or non-CNS embolism
First major bleeding event
MACNE (composite MI, SSE, TIA, CV death)
All-cause death
Statistical Analysis:
For baseline characteristics; Chi-square test was used to compare categorical variables and Wilcoxon rank-sum to compare continuous variables
Cox frailty model was used for multivariate adjustment
2. In this population of 9,319 patients with AF, 38% were asymptomatic at baseline and both symptom classifications identified asymptomatic patients in similar fashion
3. There were no major differences in risk of stroke/non-CNS embolism, major bleeding, MACNE, and all cause death between asymptomatic and symptomatic patients with AF
LIMITATIONS
This is an observational analysis and is subject to the risk of confounding despite adjustment for a large number of covariates
Patients included in this study were selected from outpatient practices, so these results may not be generalizable to an inpatient population or untreated populations who do not attend outpatient clinics
The AF patients enrolled in this registry had clinically identified AF and therefore may have had symptoms at the time of initial diagnosis, prior to enrolment
Hypotheses generated by this analysis of patients with known asymptomatic or symptomatic AF with regard to the association of symptoms with outcomes may not be applicable to a population of patients with untreated, undiagnosed subclinical AF
CONCLUSIONS
A similar risk of thromboembolic events, bleeding, and death was observed in patients with asymptomatic versus symptomatic AF
Prospective, randomized studies are needed to further define associated adverse events and delineate optimal prophylactic therapies in patients with asymptomatic AF
ACKNOWLEDGEMENTS
2. Reiffel JA, Verma A, Kowey PR, et al. Incidence of Previously Undiagnosed Atrial Fibrillation Using Insertable Cardiac Monitors in a High-Risk Population: The REVEAL AF Study. JAMA Cardiol. August doi: /jamacardio
REFERENCES:
3. Nasir JM, Pomeroy W, Marler A, et al. Predicting Determinants of Atrial Fibrillation or Flutter for Therapy Elucidation in Patients at Risk for Thromboembolic Events (PREDATE AF) Study. Heart Rhythm. 2017;14(7): doi: /j.hrthm
1. 1. Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med. 2012;366(2): doi: /NEJMoa
4. Healey JS, Alings M, Ha AC, et al. Subclinical Atrial Fibrillation in Older Patients. Circulation. August doi: /CIRCULATIONAHA
Conflict of Interest Disclosures:
The ORBIT-AF registry was sponsored by Janssen Scientific Affairs, LLC. Dr. Fonarow has received consultancy fees from Janssen and Medtronic. Dr. Gersh has received personal fees from Mount Sinai–St Luke’s, Boston Scientific Corp, Janssen Scientific Affairs, St Jude Medical, Baxter Healthcare Corp, Cardiovascular Research Foundation, Medtronic, Xenon Pharmaceuticals, Cipla Ltd, Thrombosis Research Institute, and Armetheon Inc. Dr. Kenneth W. Mahaffey’s financial disclosures can be viewed at Dr. Peterson has received personal fees from Boehringer Ingelheim, Sanofi, AstraZeneca, Valeant, and Bayer; grants and personal fees from Janssen; and research support from Eli Lilly & Co and Janssen Scientific Affairs. Dr. Piccini received a grant from Janssen Pharmaceuticals; consulting fees from Bristol-Myers Squibb/Pfizer and Johnson & Johnson; research support from ARCA Biopharma, Boston Scientific, GE Healthcare, and Johnson & Johnson/Janssen Scientific Affairs; and consultancy fees from Forest Laboratories, Janssen Scientific Affairs, Pfizer/Bristol-Myers Squibb, Spectranetics, and Medtronic. Dr. Kowey is a consultant for and advisory board member with Boehringer Ingelheim, Bristol-Myers Squibb, Johnson & Johnson, Portola, Merck, Sanofi, Daiichi-Sankyo, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.