Screening of implantable loop recorders (ILR) can result in a 3-fold increase in detection of atrial fibrillation and the 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 evident from research published in the Lancet.
In the absence of evidence of the health benefits of atrial fibrillation screening, researchers sought to determine whether systematic, intensive atrial fibrillation screening and the use of anticoagulants could prevent stroke in a population of high-risk patients.
The LOOP study (ClinicalTrials.gov Identifier: NCT02036450) is a investigator-initiated, multicenter, open-label, randomized controlled study at 4 centers in Denmark. Participants were between 70 and 90 years old and had either high blood pressure, diabetes, stroke, or heart failure and had no atrial fibrillation, a history of atrial fibrillation, no pacemaker, or were taking anticoagulant medication, or were contraindicated to anticoagulation.
Participants were randomly assigned in a 1: 3 ratio to either the intervention group – who received an ILR – or the control group who received the usual care. Baseline assessments were performed for detailed medical history, medication prescriptions, vital signs, and blood samples. ILR implantation took place 4 weeks after randomization, and all participants in this group were followed up daily using automated continuous ECG monitoring. When atrial fibrillation lasting 6 minutes was detected, patients were contacted and recommended that oral anticoagulation therapy be initiated.
The primary study result was a composite endpoint of stroke or systematic arterial embolism. Secondary endpoints included the composite endpoint ischemic stroke, transient ischemic attack, or systemic arterial embolism; the composite endpoint of stroke, systemic arterial embolism, or cardiovascular death; cardiovascular death; and death of all kinds.
A total of 6004 patients screened between 2014 and 2016 were included in the study: 1501 (25%) in the ILR group and 4503 (75%) in the control group. The mean age of the participants was 74.7 ± 4.1 years and 47.3% were women.
In the ILR group, 94.6% of the participants received ILR, with a median time from randomization to implantation of 24 days (interquartile range [IQR], 27-35). The median duration of follow-up was 39.3 months (IQR, 8-41.5). ILR monitoring was terminated prematurely in 11.7% of the subjects, and no participant in the control group received ILR during the study.
Follow-up data were available for all outcomes through January 28, 2021, and no participants were lost for follow-up. The median follow-up was 64.5 months (IQR, 59.3-69.8). The investigators diagnosed atrial fibrillation in 31.8% and 12.2% of the participants in the ILR and the control group (hazard ratio [HR], 3.17; 95% CI, 2.81-3.59). In the ILR group, 89.3% of patients were diagnosed with atrial fibrillation within 3 years of randomization (versus 49.3% in the control group).
A total of 29.7% and 13.1% of the 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 patients with atrial fibrillation started oral anticoagulation therapy within the first 3 months; 96.5% initiated it at any time.
A total of 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); the median time from onset to discontinuation was 16.8 months (IQR, 2.73-31.5).
A total of 318 participants experienced the primary outcome of a stroke or systemic arterial embolism (269 ischemic strokes, 40 hemorrhagic strokes, 6 unspecified strokes and 3 systemic arterial embolisms): 4.5% in the ILR group and 5.6% in the of the control group, equal to 0.88 and 1.09 events per 100 person-years, respectively. No significant difference was found between the groups (HR 0.80; 95% CI 0.61-1.05).
Within the ILR group, 17 participants suffered a stroke or systemic embolism after the onset of atrial fibrillation; 88.2% of these patients had already started oral anticoagulation, most episodes were short-lived, 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 (versus 3.5% in the control group; HR 1.00; 95% CI 0.84-1.19).
The results of the first sensitivity analysis of the primary endpoint – which included only participants who received the assigned intervention at randomization – identified 316 cases of the primary endpoint (HR, 0.81; 95% CI, 0.62-1.07) . The results of a second sensitivity analysis, in which participants were censored who had prematurely discontinued ILR monitoring with no result, atrial fibrillation or death, identified 207 cases with a primary endpoint (HR 0.70; 95% CI 0.52-0.94) .
With the exception of systolic blood pressure, there were no significant treatment-subgroup interactions for the pre-established baseline variables. Among participants with the highest tertile systolic blood pressure (≥157 mmHg), the primary endpoint rate in the ILR group was significantly lower (HR 0.51; 95% CI 0.31-0.83). In participants in the middle and lowest systolic blood pressure tertile (141-156 mmHg and <141 mmHg), the primary endpoints between the ILR and control groups did not differ significantly (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 resulting in device explantation; The median time from implantation to explantation was 40 days (IQR, 22-51). Eight of these participants received a new implant to resume remote monitoring. Other adverse events included major bleeding (4.3% and 3.5% of the ILR and control groups, respectively) and hemorrhagic stroke (0.8% and 0.8%, respectively).
Limitations of the study include the use of registries to identify and recruit potential participants, which can create bias in healthy users, and the fact that asymptomatic atrial fibrillation is detected in both short- and long-term episodes.
“In this study of people at high risk of stroke, screening for atrial fibrillation using continuous long-term monitoring by the ILR resulted in a 3-fold increase in [the] Detection of atrial fibrillation and simultaneous anticoagulation, but no significant reduction in the risk of stroke or systemic arterial embolism, ”the researchers concluded.
Disclosure: Several study authors stated links with the pharmaceutical industry. For a full list of the author’s disclosures, see the original reference.
Svendsen JH, Diederichesen SZ, Højberg S, et al. Implantable Loop Recorder for Detecting Atrial Fibrillation to Prevent Stroke (The LOOP Study): A Randomized Controlled Study. Lancet. Published online 29 August 2021. doi: 10.1016 / S0140-6736 (21) 01698-6
This article originally appeared on The Cardiology Advisor