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Original Investigation
September 29, 2021

Temporal Association Between Episodes of Atrial Fibrillation and Risk of Ischemic Stroke

Author Affiliations
  • 1Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital, Boston
  • 2Medtronic, Mounds View, Minnesota
  • 3Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
JAMA Cardiol. Published online September 29, 2021. doi:10.1001/jamacardio.2021.3702
Key Points

Question  What is the temporal association between episodes of atrial fibrillation (AF) and ischemic stroke in patients with cardiac implantable electronic devices (CIEDs)?

Findings  In this case-crossover study including 891 patients with CIEDs and ischemic stroke, multihour AF episodes raised the odds of stroke 3.7-fold for up to 30 days. The risk of stroke was highest within 5 days of the AF episode and decreased rapidly thereafter.

Meaning  In patients with CIEDs, multihour episodes of AF were temporally associated with a transient increase in the risk of stroke; these findings support a study of time-delimited anticoagulation in patients with infrequent multihour episodes of AF.


Importance  Understanding the temporal association between atrial fibrillation (AF) and ischemic stroke informs our understanding of the AF-stroke mechanism and treatment of paroxysmal AF.

Objective  To define the temporal association between episodes of AF and stroke in patients with cardiac implantable electronic devices (CIEDs).

Design, Setting, and Participants  In this case-crossover study, data from a large national electronic health record database were linked with a single-vendor database of heart rhythm records of patients with CIEDs capable of continuous heart rhythm monitoring. Patients with CIEDs who sustained an ischemic stroke who also had 120 days of continuous remote rhythm monitoring prestroke were included. Data were collected from January 2007 to March 2017, and data were analyzed from November 2019 to June 2020.

Exposure  AF for 5.5 hours or more on any given day during days 1 to 30 vs days 91 to 120 prestroke.

Main Outcomes and Measures  Odds ratio for stroke comparing AF during days 1 to 30 vs 91 to 120 prestroke. This analysis was planned prior to the study.

Results  From 466 635 patients included in both the Optum electronic health record and CareLink databases, 891 patients with CIEDs and ischemic stroke with continuous monitoring in the 120 days prestroke were identified. Of 891 included patients, 575 (64.5%) were male, and the median (interquartile range) age was 76 (67-82) years. The vast majority of patients with stroke had either no AF meeting the threshold duration of 5.5 hours or more in both the case and control periods (682 of 891 [76.5%]) or AF of 5.5 hours or more in both periods (143 of 891 [16.0%]). For those not meeting the 5.5-hour AF threshold in either period, there was no or very little AF throughout the 120 days prestroke. A total of 66 patients had informative, discordant arrhythmic states, with 52 having AF of 5.5 hours or more in the case period vs 14 in the control period (odds ratio [OR], 3.71; 95% CI, 2.06-6.70). Stroke risk was increased most in days 1 to 5 following an AF episode (OR, 5.00; 95% CI, 2.62-9.55). AF greater than 23 hours on a given day was associated with the clearest increase in stroke risk (OR, 5.00; 95% CI, 2.08-12.01).

Conclusions and Relevance  In this large cohort of patients with CIEDs and continuous rhythm monitoring prior to ischemic stroke, excess stroke risk above baseline was highest within 5 days of an episode of AF of 5.5 hours or more in duration and diminished rapidly thereafter. Our findings are consistent with the traditional view that AF is directly and transiently associated with ischemic stroke. These results provide support for trials of time-delimited anticoagulation for patients with infrequent multihour episodes of AF and rigorous, continuous rhythm monitoring.

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