Association of Burden of Atrial Fibrillation With Risk of Ischemic Stroke in Adults With Paroxysmal Atrial Fibrillation: The KP-RHYTHM Study

Abstract

Importance: Atrial fibrillation is a potent risk factor for stroke, but whether the burden of atrial fibrillation in patients with paroxysmal atrial fibrillation independently influences the risk of thromboembolism remains controversial.

Objective: To determine if the burden of atrial fibrillation characterized using noninvasive, continuous ambulatory monitoring is associated with the risk of ischemic stroke or arterial thromboembolism in adults with paroxysmal atrial fibrillation.

Design, setting, and participants: This retrospective cohort study conducted from October 2011 and October 2016 at 2 large integrated health care delivery systems used an extended continuous cardiac monitoring system to identify adults who were found to have paroxysmal atrial fibrillation on 14-day continuous ambulatory electrocardiographic monitoring.

Exposures: The burden of atrial fibrillation was defined as the percentage of analyzable wear time in atrial fibrillation or flutter during the up to 14-day monitoring period.

Main outcomes and measures: Ischemic stroke and other arterial thromboembolic events occurring while patients were not taking anticoagulation were identified through November 2016 using electronic medical records and were validated by manual review. We evaluated the association of the burden of atrial fibrillation with thromboembolism while not taking anticoagulation after adjusting for the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) or CHA2DS2-VASc stroke risk scores.

Results: Among 1965 adults with paroxysmal atrial fibrillation, the mean (SD) age was 69 (11.8) years, 880 (45%) were women, 496 (25%) were persons of color, the median ATRIA stroke risk score was 4 (interquartile range [IQR], 2-7), and the median CHA2DS2-VASc score was 3 (IQR, 1-4). The median burden of atrial fibrillation was 4.4% (IQR ,1.1%-17.23%). Patients with a higher burden of atrial fibrillation were less likely to be women or of Hispanic ethnicity, but had more prior cardioversion attempts compared with those who had a lower burden. After adjusting for either ATRIA or CHA2DS2-VASc stroke risk scores, the highest tertile of atrial fibrillation burden (≥11.4%) was associated with a more than 3-fold higher adjusted rate of thromboembolism while not taking anticoagulants (adjusted hazard ratios, 3.13 [95% CI, 1.50-6.56] and 3.16 [95% CI, 1.51-6.62], respectively) compared with the combined lower 2 tertiles of atrial fibrillation burden. Results were consistent across demographic and clinical subgroups.

Conclusions and relevance: A greater burden of atrial fibrillation is associated with a higher risk of ischemic stroke independent of known stroke risk factors in adults with paroxysmal atrial fibrillation.

Figure 1.. Eligible Adults With Paroxysmal Atrial Fibrillation Found on Continuous Ambulatory Electrocardiographic (ECG) Monitoring

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Figure 2.. Distribution of Atrial Fibrillation (AF) Burden Found on Continuous Ambulatory Electrocardiographic Monitoring Among 1965 Adults With Confirmed Paroxysmal AF

Figure 3.. Thromboembolic Event Rates While Not Taking Anticoagulation, Overall and Stratified by Atrial Fibrillation (AF) Burden Tertile in 1965 Adults With Confirmed Paroxysmal AF

Overall, there were 29 thromboembolic events for 1915 person-years. In tertile 1, there were 5 events over 690 person-years in which patients spent 0.01%-2.03% of time in AF or atrial flutter. In tertile 2, there were 7 events over 639 person-years in which patients spent 2.05%-11.28% of time in AF or atrial flutter. In tertile 3, there were 17 events over 586 person-years in which patients spent 11.36%-99.99% of time in AF or atrial flutter.

Figure 4.. Association Between Atrial Fibrillation (AF) Burden and Thromboembolic Events While Not Taking Anticoagulation in Adults With Confirmed Paroxysmal AF

A, Unadjusted and multivariable-adjusted results for the cumulative burden of AF and the duration of the longest episode of AF in the overall cohort. B, Results of the cumulative burden of AF and thromboembolism in prespecified patient subgroups with adjustment for Anticoagulation and Risk Factors in Atrial Fibrillation risk score. Given the distribution of AF burden by diabetes status, a model estimate was not possible in the subgroup with diabetes.