Effect of Long-term Continuous Cardiac Monitoring vs Usual Care on Detection of Atrial Fibrillation in Patients With Stroke Attributed to Large- or Small-Vessel Disease: The STROKE-AF Randomized Clinical Trial

Abstract

Importance: Patients with ischemic stroke attributed to large- or small-vessel disease are not considered at high risk for atrial fibrillation (AF), and the AF incidence rate in this population is unknown.

Objectives: To determine whether long-term cardiac monitoring is more effective than usual care for AF detection in patients with stroke attributed to large- or small-vessel disease through 12 months of follow-up.

Design, setting, and participants: The STROKE-AF trial was a randomized (1:1), multicenter (33 sites in the US) clinical trial that enrolled 496 patients between April 2016 and July 2019, with primary end point follow-up through August 2020. Eligible patients were aged 60 years or older or aged 50 to 59 years with at least 1 additional stroke risk factor and had an index stroke attributed to large- or small-vessel disease within 10 days prior to insertable cardiac monitor (ICM) insertion.

Interventions: Patients randomized to the intervention group (n = 242) received ICM insertion within 10 days of the index stroke; patients in the control group (n = 250) received site-specific usual care consisting of external cardiac monitoring, such as 12-lead electrocardiograms, Holter monitoring, telemetry, or event recorders.

Main outcomes and measures: Incident AF lasting more than 30 seconds through 12 months.

Results: Among 492 patients who were randomized (mean [SD] age, 67.1 [9.4] years; 185 [37.6%] women), 417 (84.8%) completed 12 months of follow-up. The median (interquartile range) CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, sex category) score was 5 (4-6). AF detection at 12 months was significantly higher in the ICM group vs the control group (27 patients [12.1%] vs 4 patients [1.8%]; hazard ratio, 7.4 [95% CI, 2.6-21.3]; P < .001). Among the 221 patients in the ICM group who received an ICM, 4 (1.8%) had ICM procedure-related adverse events (1 site infection, 2 incision site hemorrhages, and 1 implant site pain).

Conclusions and relevance: Among patients with stroke attributed to large- or small-vessel disease, monitoring with an ICM compared with usual care detected significantly more AF over 12 months. However, further research is needed to understand whether identifying AF in these patients is of clinical importance.

Trial registration: ClinicalTrials.gov Identifier: NCT02700945.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Bernstein reported receiving grants from Northwestern University during the conduct of the study and personal fees from Medtronic outside the submitted work, and performing consulting and steering committee work with Boehringer Ingelheim Pharmaceuticals related to Pradaxa, atrial fibrillation, and cryptogenic stroke and consulting and speaking for Abbott related to patent foramen ovale closure. Dr Kamel reported serving as a principal investigator for the National Institutes of Health–funded ARCADIA trial (NINDS U01NS095869), which receives in-kind study drug from the BMS-Pfizer Alliance for Eliquis and ancillary study support from Roche Diagnostics, serving as deputy editor for JAMA Neurology, serving as a steering committee member of Medtronic's Stroke-AF trial (uncompensated), and serving on an end point adjudication committee for a trial of empagliflozin for Boehringer Ingelheim. Dr Granger reported receiving personal fees from Medtronic during the conduct of the study and personal fees from Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Janssen Pharmaceuticals, and Pfizer and research grants from Medtronic Foundation, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Janssen Pharmaceuticals, and Pfizer. Dr Piccini reported receiving grants from Abbott, Boston Scientific, Bayer, and AHA and personal fees from Biotronik, Medtronic, and Pfizer outside the submitted work. Dr Sethi reported receiving speaker fees and honorarium from Medtronic during the conduct of the study and honorarium from WL Gore outside the submitted work. Dr Katz reported receiving grants from Medtronic during the conduct of the study and grants from Siemens Healthineers and the National Institutes of Health/National Institute of Neurological Disorders and Stroke (NINDS) outside the submitted work. Dr Alfaro Vives reported being an employee of and shareholder in Medtronic outside the submitted work. Dr Ziegler reported being an employee of and shareholder in Medtronic outside the submitted work. Dr Franco reported receiving personal fees from and being an employee of and shareholder in Medtronic outside the submitted work. Dr Schwamm reported receiving grants from Medtronic as the national co–primary investigator of the Stroke-AF trial during the conduct of the study and grants from Genentech, which supplied alteplase free of charge to Massachusetts General Hospital as well as supplemental per-patient payments to participating sites in our NINDS-funded trial; grants from NINDS as the national co–primary investigator in a late-window thrombolysis trial (P50NS051343, MR WITNESS NCT01282242) and as the site primary investigator of StrokeNet Network NINDS (New England Regional Coordinating Center U24NS107243); and personal fees from Genentech as a scientific consultant regarding trial design and conduct (late window thrombolysis) and a member of steering committee (TIMELESS NCT03785678), LifeImage as a consultant on user interface design and usability for teleradiology, Penumbra as a member of a data safety monitoring board (MIND NCT03342664), and Diffusion Pharma as a member of a data and safety monitoring board (PHAST-TSC NCT03763929) outside the submitted work.

Figures

Figure 1.. Patient Flow in a Study of Long-term Continuous Cardiac Monitoring vs Usual Care on Detection of Atrial Fibrillation in Patients With Stroke Attributed to Large- or Small-Vessel Disease

ICM indicates insertable cardiac monitor. aSites were not required to provide screening logs during the recruitment phase; therefore, the number of patients initially screened and reasons preventing their enrollment are not available.

Figure 2.. Time to First Detection of Atrial Fibrillation at 12 Months in a Study of Long-term Continuous Cardiac Monitoring vs Usual Care on Detection of Atrial Fibrillation (AF) in Patients With Stroke Attributed to Large- or Small-Vessel Disease

At 6 months, the AF incidence was 7.9% in the ICM group vs 0.8% in the control group (hazard ratio, 9.9 [95% CI, 2.3-43.5]; P < .001). The median (interquartile range) time from randomization to AF detection was 99 (36.0-235.0) days for the insertable cardiac monitor (ICM) group and 181 (86.0-231.0) days for the control group. The median (interquartile range) observation time was 365 (365-365) days for all randomized patients for each group.

Figure 3.. Time to First Detection of Atrial Fibrillation at 12 Months in a Study of Long-term Continuous Cardiac Monitoring vs Usual Care in Patients With Stroke Attributed to Large- or Small-Vessel Disease

The median (interquartile range) observation time was 365 (365-365) days for all randomized patients for each group. ICM indicates insertable cardiac monitor.

Figure 4.. Rate of Recurrent Stroke at 12 Months in a Study of Long-term Continuous Cardiac Monitoring vs Usual Care on Detection of Atrial Fibrillation in Patients With Stroke Attributed to Large- or Small-Vessel Disease

The median (interquartile range) observation time was 365 (365-365) days for all randomized patients for each group. ICM indicates insertable cardiac monitor.