Implantable loop recorder (ILR) device screening may lead to a 3-fold increase in detection of atrial fibrillation and initiation of necessary oral anticoagulation therapy, but does not significantly reduce the risk of stroke or systemic arterial embolism in high-risk patients. This is according to research results published in the Lancet.
Due to the dearth of evidence on the health benefits of atrial fibrillation screening, researchers sought to determine whether systematic, intensive atrial fibrillation screening and anticoagulant use can prevent stroke in a population of high-risk individuals.
The LOOP Study (ClinicalTrials.gov Identifier: NCT02036450) is an investigator-initiated, multicenter, unblinded, randomized controlled trial at 4 centers in Denmark. Participants were between 70 and 90 years of age and had either hypertension, diabetes, previous stroke, or heart failure and did not have atrial fibrillation, a history of atrial fibrillation, or a pacemaker, or take anticoagulation medicine or be contraindicated to anticoagulation.
Participants were randomly assigned 1:3 to either the intervention group—who received an ILR—or the control group, who received usual care. Baseline assessments were undertaken for a detailed medical history, drug prescriptions, vital signs, and blood samples. ILR implantation took place 4 weeks after randomization, and all participants in this group were followed up via automated continuous ECG monitoring on a day-to-day basis. If atrial fibrillation of 6-minute duration was detected, patients were contacted and recommended to begin oral anticoagulation therapy.
The primary study outcome was a combined endpoint of stroke or systematic arterial embolism. Secondary outcomes included the combined endpoint of ischemic stroke, transient ischemic attack, or systemic arterial embolism; the combined endpoint of stroke, systemic arterial embolism, or cardiovascular death; cardiovascular death; and all-cause death.
A total of 6004 patients screened between 2014 and 2016 were included in the study: 1501 (25%) to the ILR group and 4503 (75%) to the control group. Mean participant age was 74.7±4.1 years and 47.3% were women.
In the ILR group, 94.6% of participants received ILR, with a median time from randomization to implantation of 24 days (interquartile range [IQR], 27-35). Median monitoring duration was 39.3 months (IQR, 8-41.5). Premature discontinuation of ILR monitoring took place in 11.7% of individuals, and no control group participants received ILR during the trial.
For all outcomes, follow-up data were available until January 28, 2021, with no participants lost to follow-up. The median follow-up period was 64.5 months (IQR, 59.3-69.8). Investigators diagnosed atrial fibrillation in 31.8% and 12.2% of ILR and control group participants (hazard ratio [HR], 3.17; 95% CI, 2.81-3.59). In the ILR group, 89.3% of those with atrial fibrillation were diagnosed within 3 years of randomization (vs 49.3% of the control group).
A total of 29.7% and 13.1% of patients in the ILR and control groups initiated oral anticoagulation therapy (HR, 2.72; 95% CI, 2.41-3.08). In the ILR group, 78.6% of those with atrial fibrillation initiated oral anticoagulation therapy within the first 3 months; 96.5% initiated it at any time.
Overall, 4.6% of 910 patients with atrial fibrillation who initiated oral anticoagulation therapy discontinued treatment (5.8% in the ILR group and 3.6% in the control group); median time from initiation to discontinuation was 16.8 months (IQR, 2.73-31.5).
In total, 318 participants experienced the primary outcome of stroke or systemic arterial embolism (269 ischemic stroke, 40 hemorrhagic stroke, 6 unspecified stroke, and 3 systemic arterial embolism): 4.5% in the ILR group and 5.6% in the control group, equal to 0.88 and 1.09 events per 100 person-years, respectively. No significant between-group difference was noted (HR, 0.80; 95% CI, 0.61-1.05).
Within the ILR group, 17 participants had a stroke or systemic embolism after atrial fibrillation began; 88.2% of these patients had already initiated oral anticoagulation, most episodes were short-lasting, and the time from atrial fibrillation to stroke ranged from 0 to 42 months.
Cardiovascular death was noted in 2.9% of participants in the ILR group (vs 3.5% in the control group; HR, 1.00; 95% CI, 0.84-1.19).
Results of the first sensitivity analysis of the primary outcome—which included only participants who received the assigned intervention at randomization—identified 316 instances of the primary outcome (HR, 0.81; 95% CI, 0.62-1.07). Results of a second sensitivity analysis, which censored participants who had premature discontinuation of ILR monitoring without outcome, atrial fibrillation, or death identified 207 primary outcome instances (HR, 0.70; 95% CI, 0.52-0.94).
There were no significant treatment-by-subgroup interactions across prespecified baseline variables, with the exception of systolic blood pressure. Among participants with the highest tertile of systolic blood pressure (≥157 mmHg), the primary outcome rate was significantly lower in the ILR group (HR, 0.51; 95% CI, 0.31-0.83). In participants in the middle and lowest systolic blood pressure tertiles (141-156 mmHg and <141 mmHg), the primary outcome rates were not significantly different between the ILR and control groups (HRs, 1.06-0.99; 95% CI, 0.68-1.67 and 0.62-1.57).
Of the 1420 participants who received an ILR device, 0.6% reported complications leading to device explantation; time from implantation to explantation was a median of 40 days (IQR, 22-51). Eight of these participants had a new implantation in order to resume remote monitoring. Other adverse events included major bleeding (4.3% and 3.5% of the ILR and control groups) and hemorrhagic stroke (0.8% and 0.8%, respectively).
Study limitations include the use of registries to identify and recruit potential participants, which may introduce healthy user bias, and the reality of detecting asymptomatic atrial fibrillation in both short- and long-term episodes.
“In this trial of individuals at high risk of stroke, screening for atrial fibrillation using long-term continuous monitoring by ILR resulted in a 3-times increase in [the] detection of atrial fibrillation and concomitant anticoagulation, but no significant decrease in the risk of stroke or systemic arterial embolism,” the researchers concluded.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Svendsen JH, Diederichesen SZ, Højberg S, et al. Implantable loop recorder detection of atrial fibrillation to prevent stroke (The LOOP Study): A randomized controlled trial. Lancet. Published online August 29, 2021. doi:10.1016/S0140-6736(21)01698-6