Effect of Implantable vs Prolonged External Electrocardiographic Monitoring on Atrial Fibrillation Detection in Patients With Ischemic Stroke: The PER DIEM Randomized Clinical Trial

Abstract

Importance: The relative rates of detection of atrial fibrillation (AF) or atrial flutter from evaluating patients with prolonged electrocardiographic monitoring with an external loop recorder or implantable loop recorder after an ischemic stroke are unknown.

Objective: To determine, in patients with a recent ischemic stroke, whether 12 months of implantable loop recorder monitoring detects more occurrences of AF compared with conventional external loop recorder monitoring for 30 days.

Design, setting, and participants: Investigator-initiated, open-label, randomized clinical trial conducted at 2 university hospitals and 1 community hospital in Alberta, Canada, including 300 patients within 6 months of ischemic stroke and without known AF from May 2015 through November 2017; final follow-up was in December 2018.

Interventions: Participants were randomly assigned 1:1 to prolonged electrocardiographic monitoring with either an implantable loop recorder (n = 150) or an external loop recorder (n = 150) with follow-up visits at 30 days, 6 months, and 12 months.

Main outcomes and measures: The primary outcome was the development of definite AF or highly probable AF (adjudicated new AF lasting ≥2 minutes within 12 months of randomization). There were 8 prespecified secondary outcomes including time to event analysis of new AF, recurrent ischemic stroke, intracerebral hemorrhage, death, and device-related serious adverse events within 12 months.

Results: Among the 300 patients who were randomized (median age, 64.1 years [interquartile range, 56.1 to 73.7 years]; 121 were women [40.3%]; and 66.3% had a stroke of undetermined etiology with a median CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, sex category] score of 4 [interquartile range, 3 to 5]), 273 (91.0%) completed cardiac monitoring lasting 24 hours or longer and 259 (86.3%) completed both the assigned monitoring and 12-month follow-up visit. The primary outcome was observed in 15.3% (23/150) of patients in the implantable loop recorder group and 4.7% (7/150) of patients in the external loop recorder group (between-group difference, 10.7% [95% CI, 4.0% to 17.3%]; risk ratio, 3.29 [95% CI, 1.45 to 7.42]; P = .003). Of the 8 specified secondary outcomes, 6 were not significantly different. There were 5 patients (3.3%) in the implantable loop recorder group who had recurrent ischemic stroke vs 8 patients (5.3%) in the external loop recorder group (between-group difference, -2.0% [95% CI, -6.6% to 2.6%]), 1 (0.7%) vs 1 (0.7%), respectively, who had intracerebral hemorrhage (between-group difference, 0% [95% CI, -1.8% to 1.8%]), 3 (2.0%) vs 3 (2.0%) who died (between-group difference, 0% [95% CI, -3.2% to 3.2%]), and 1 (0.7%) vs 0 (0%) who had device-related serious adverse events.

Conclusions and relevance: Among patients with ischemic stroke and no prior evidence of AF, implantable electrocardiographic monitoring for 12 months, compared with prolonged external monitoring for 30 days, resulted in a significantly greater proportion of patients with AF detected over 12 months. Further research is needed to compare clinical outcomes associated with these monitoring strategies and relative cost-effectiveness.

Trial registration: ClinicalTrials.gov Identifier: NCT02428140.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Buck reported receiving research funding from Alberta Innovates Health Solutions. Dr Hill reported receiving grants from NoNO Inc, Boehringer Ingelheim Canada, Medtronic LLC; receiving personal fees from Sun Pharma; being involved in a US patent licensed to Circle Neurovascular Inc; and serving as director for Circle Neurovascular Inc, the Canadian Stroke Consortium, and the Canadian Neuroscience Federation. Dr Quinn reported receiving personal fees from Bristol-Myers Squibb/Pfizer; and receiving grants from Bayer. Dr Butcher reported receiving personal fees from Medtronic, Boehringer-Ingelheim, Servier, Bayer, and Bristol-Myers Squibb/Pfizer; and receiving grants or other research funding from Boehringer-Ingelheim, Bayer, Pfizer, Servier Canada, and Bristol-Myers Squibb/Pfizer. Dr Menon reported holding shares in Circle NVI. Dr Smith reported receiving consulting fees from Alnylam, Biogen, Bayer, and Javelin; and receiving royalties from UpToDate. Dr Jickling reported receiving grants from the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada. Dr Kamal reported receiving personal fees for serving as part owner of DESTINE Health Inc; and receiving grants from the Canadian Institutes of Health Research. Dr Demchuk reported receiving personal fees from Bristol-Myers Squibb/Pfizer. Dr Exner reported being chief medical officer and minority shareholder in HelpWear Inc; receiving consulting fees and research funding from Abbott Medical, Boston Scientific, GE Healthcare, and Medtronic Inc; and receiving nonfinancial support and having stock options in Analytics for Life. No other disclosures were reported.

Figures

Figure 1.. Flowchart of Randomization, Device Allocation, and Follow-up of Patients Enrolled in the PER DIEM Randomized Clinical Trial

PER DIEM indicates Post-Embolic Rhythm Detection with Implantable vs External Monitoring. aThe study sites were not required to maintain screening logs thus the total number of patients assessed for study eligibility was not available. bOf the 24 patients, 5 had the device inserted. cOf the 17 patients, 10 completed more than 24 hours of monitoring.

Figure 2.. Secondary Outcome of the Probability of New Atrial Fibrillation or Flutter Lasting 2 Minutes or Longer Within 12 Months

All patients were included as randomized when calculating survival. Eight patients in each group withdrew immediately after randomization. These patients were censored at day 0. The overall median time at risk was 342 days (interquartile range, 135-258 days). There was a significant difference in the time to detection of new atrial fibrillation or flutter between the groups (age- and sex-adjusted hazard ratio, 3.36 [95% CI, 1.44-7.84], P = .005; log-rank test P = .002).