Reviwer : Dr. İbrahim Rencüzoğulları

Name of the study : Detection of Atrial Fibrillation with Implantable Loop Recorder in Prevention of Stroke (The LOOP Study): A Randomized Controlled Study

Published in Congress: ESC 2021

Link: https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(21)01698-6.pdf

Introduction:

The risk of stroke is five times higher in people with atrial fibrillation (AF) than in those without. In addition, strokes secondary to AF are associated with worse outcomes than strokes that develop in the absence of AF. Although AF is associated with a 3-fold increased mortality, a significant proportion of AF patients are asymptomatic and not diagnosed with AF. Although oral anticoagulation is quite effective in the prevention of stroke in patients with AF diagnosed, a significant portion of stroke patients is undiagnosed AF patients.

Objective:

The aim of this study is to investigate whether (i) continuous monitoring in individuals at high risk and (ii) initiation of oral anticoagulation, if AF is detected, prevents stroke in individuals who have not been diagnosed with AF.

Method:

This study, in which 4 centers from Denmark participated, is a randomized controlled study created by compiling the participants from the registry. Patients with stroke risk factors (aged between 70 and 90 years, hypertension, diabetes mellitus, heart failure, having at least one of the previous stroke risk factors) but without known AF were included in the study. Patients were randomized 1:3 into the implantable loop recorder (ILR) and control (standard care) groups. Anticoagulation was recommended for AF attacks lasting >6 minutes in the ILR group. The primary outcome of the study was determined as time to first stroke or systemic arterial embolism. Secondary outcomes of the study were: (1) composite endpoint of ischemic stroke, transient ischemic attack, or systemic arterial embolism; (2) the composite endpoint of stroke, systemic arterial embolism, or cardiovascular death; (3) cardiovascular death; and (4) all-cause death.

Results:

6004 out of 6205 patients screened between 2014 and 2016 were included in the study. 1501 (25.0%) were randomized to the ILR group and 4503 (75.0%) to the control group. The mean age was 74.7 years and 47.3% of the patients were female. Total observation time with ILR in the ILR group was 3.3 years, while the median follow-up time for all patients was 64.5 months (IQR 59.3-69.8).

AF was observed in a total of 1027 patients; 477 (32%) vs. ILR group. 550 (12%) in the control group (HR 3.17; 95% CI 2.81–3.59; p<0·0001)

Oral anticoagulation was started in 1036 patients. 445 (29.7%) vs. ILR group. 591 (13.1%) in the control group (HR 2.72 95% CI 2.41-3.08; p <0.0001) (91% of patients with AF in the ILR group and 87% of patients with AF in the control group were started on anticoagulants).

The primary end-point occurred in 318 participants (315 strokes, three systemic arterial embolisms): 67 (4.5%) in the ILR group vs. 251 (5.6%) in the control group (HR 0.80 95% CI 0.61–1.05; p=0.11).

In the secondary outcomes of the study, the results of the ILR group and the control group were similar (p>0.05).

Major bleeding occurred in 221 participants: 65 (4.3%) in the ILR group vs 156 (3.5%) in the control group (HR 1.26 95% CI 0.95–1.69; p=0.11).

Conclusion:

Although ILR scanning increased the detection of AF and initiation of anticoagulation threefold in patients with stroke risk factors, there was no significant reduction in the risk of stroke or systemic arterial embolism. Although AF was detected in 30% of the participants in the ILR group and anticoagulants were started in 91% of the patients with AF, the reduction in the risk of primary outcome was only 20% and was not statistically significant. 62 patients had to be screened with ILR for a primary outcome reduction (Number needed to screen:62). These findings may mean that not all AFs are worth screening with ILR and that AF detected in all scans do not deserve anticoagulation.

Interpretation :

In this study, although it was demonstrated that ILR is effective in detecting AF and initiating anticoagulants in patients with high stroke risk, but ineffective in primary and secondary outcomes; Defining the presence of AF as >6 minutes in the ILR group, defining AF only as present or absent, ignoring the AF burden, initiating treatment in AF and not evaluating the compliance of the patients to treatment can be considered as important deficits in the study. In the per-protocol analysis, it should not be ignored that screening with ILR is effective in preventing primary outcome compared to the control group.