More thorough cardiac monitoring after stroke meant more subclinical atrial fibrillation (AFib) was detected, trial data from two studies published in JAMA showed.
“Based on the findings of the STROKE-AF trial and the PER DIEM trial reported in this issue of JAMA, combined with existing evidence, it seems that (1) there is a substantial amount of subclinical AFib detectable after non–AFib-related ischemic stroke, and not just among patients with embolic stroke of undetermined source, (2) the longer patients are monitored, the more subclinical AFib will be detected, and (3) the more subclinical AFib detected, the greater the risk of stroke,” wrote David Tirschwell, MD, MSc, and Nazem Akoum, MD, MS, both of the University of Washington in Seattle, in an editorial accompanying the studies.
“What remains missing is an evidence-based threshold based on the frequency and duration of subclinical AFib for initiating anticoagulation therapy,” Tirschwell and Akoum said.
Subclinical AFib consists of asymptomatic, infrequent episodes of AFib detected by implantable or external monitors. It often is not found during initial stroke workup but is seen during extended rhythm monitoring. Whether this should lead to anticoagulation in some, most, or all patients is unclear, though subclinical AFib confers increased risk of ischemic stroke proportional to its frequency and duration.
The PER DIEM trial studied patients with an index ischemic stroke and no history of AFib. Atrial fibrillation lasting 2 or more minutes occurred in 15.3% of patients with an implantable loop recorder, versus 4.7% monitored with an external loop recorder (RR 3.29, 95% CI 1.45-7.42, P=0.003), reported Brian Buck, MD, MSc, of the University of Alberta in Canada, and co-authors. “Among patients with ischemic stroke, implantable electrocardiographic monitoring for 12 months resulted in the detection of more patients with atrial fibrillation compared with prolonged external monitoring for 30 days,” the PER DIEM researchers wrote. “Further research is needed to better understand clinical outcomes and cost-effectiveness” associated with more intensive monitoring, they added.
In STROKE-AF, Richard Bernstein, MD, PhD, of Northwestern University in Chicago, and co-authors studied patients who had an index stroke attributed to large or small vessel disease randomized to 12-month follow-up with an insertable cardiac monitor versus site-specific usual care (e.g. 12-lead electrocardiogram, Holter monitors, telemetry, or event recorders). Rates of AFib for monitored versus usual care groups were 12.1% and 1.8%, respectively (HR 7.4, 95% CI 2.6-21.3, P<0.001). The STROKE-AF researchers noted that “monitoring with an insertable cardiac monitor compared with usual care detected significantly more AFib over 12 months,” and called for further research “to understand whether identifying AFib in these patients is of clinical importance.”
PER DIEM included 300 patients (median age 64, 40% women) randomized between July 2015 and November 2017 to 12-month implantable loop recorder or 30-day external loop recorder. The median CHA2DS2-VASC score, which estimates stroke risk, was 4 (the score’s range is 0-9; higher scores imply higher annual risk of stroke). Device-related serious adverse events occurred in 0% of the external recorder group and in one patient (0.7%) of the implantable recorder group, who had skin erosion requiring removal at two months.
STROKE-AF investigators reported on 492 patients with an index ischemic stroke between April 2016 and July 2019 (mean age 67, about 38% women). The median CHA2DS2-VASC score was 5. There were four procedure-related adverse events (1.8%) including one site infection, one site pain, and two incision site hemorrhages).
“The number of patients needed to monitor with an insertable cardiac monitor to detect one patient with subclinical AFib at one year is approximately 10 in both the STROKE-AF and PER DIEM trials (i.e., 100/[risk difference of approximately 10%]), which is suggestive of an effective intervention for disease detection,” Tirschwell and Akoum observed.
“However, evidence is lacking for the final link between sub-clinical AFib detection after ischemic stroke and improved clinical outcomes,” the editorialists wrote. “The gold standard test of the hypothesis that subclinical AFib detection following stroke is best managed with anticoagulation therapy would be an RCT in which all such patients were allocated to antiplatelet or anticoagulant therapy.”
AFib may be a marker of underlying pathology that is “a so-called atrial cardiopathy, as can be evidenced by such markers as left atrial enlargement on the echocardiogram, elevated P-wave terminal force on the electrocardiogram, or elevated serum natriuretic levels,” Tirschwell and Akoum pointed out. “The atrial cardiopathy construct hypothesizes atrial abnormalities that both increase the likelihood of future AFib and can directly produce cardioembolic stroke without the presence of any AFib.”
“If atrial cardiopathy could be defined and identified at the time of non–AFib-related ischemic stroke, would anticoagulation therapy be more effective than antiplatelet therapy for secondary prevention? This approach, if successful, could avoid the need for long-term heart rhythm monitoring in patients with atrial cardiopathy,” they noted, adding that this hypothesis is currently being tested the ARCADIA trial.
Limitations of the studies include potential misclassification of strokes that were embolic as due to large- or small-vessel disease in the STROKE-AF study. In PER DIEM, the median delay of two months between stroke onset and study enrollment may have decreased the rate of detection of AFib slightly.
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More thorough cardiac monitoring after stroke meant more subclinical atrial fibrillation (AFib) was detected, two studies in JAMA showed.
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Whether subclinical AFib should lead to anticoagulation in some, most, or all patients is unclear.
Paul Smyth, MD, Contributing Writer, BreakingMED™
PER DIEM was supported by Alberta Innovates Health Solutions Collaborative Research and Innovations Opportunities and by a grant from the Partnership for Research and Innovation in the Health System, government of Alberta. Buck reported receiving research funding from Alberta Innovates Health Solutions.
STROKE-AF was funded by Medtronic Inc. 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.
Tirschwell reported receiving personal fees from Abbott and serving as coprimary investigator of the National Institutes of Health StrokeNet ARCADIA study, which has received apixaban study medication from a partnership between Bristol-Myers Squibb and Pfizer. Akoum reported no disclosures.
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