Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals - LOOP

Jul 17, 2023
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Innovation Fund Denmark, The Research Foundation for the Capital Region of Denmark, The Danish Heart Foundation, Aalborg University Talent Management Program, Arvid Nilssons Fond, Skibsreder Per Henriksen, R og Hustrus Fond, The AFFECT-EU Consortium (EU Horizon 2020), Læge Sophus Carl Emil Friis og hustru Olga Doris Friis’ Legat, and Medtronic.
Date Presented:
08/29/2022
Date Published:
04/15/2023
Date Updated:
07/17/2023
Original Posted Date:
08/29/2021
References

Contribution To Literature:

Highlighted text has been updated as of July 17, 2023.

The LOOP trial showed that continuous monitoring for AF with an ILR (followed by treatment with OAC if AF was detected) was not superior to usual care in reducing stroke or systemic embolism among patients at high risk of stroke but without a known prior history of AF.

Description:

The goal of the trial was to assess the efficacy and safety of continuous monitoring for atrial fibrillation (AF) with an implantable loop recorder (ILR) versus usual care among patients at high risk for stroke without known history of AF.

Study Design

Eligible patients were randomized in an open-label 1:3 fashion to either ILR (n = 1,501) or usual care (n = 4,503). Usual care involved an annual interview with a study nurse and standard contact with the participant’s general practitioner.

  • Total screened: 6,205
  • Total number of enrollees: 6,004
  • Duration of follow-up: 64.5 months
  • Mean patient age: 74.7 years
  • Percentage female: 47%

Inclusion criteria:

  • Age 70-90 years
  • At least one of following: hypertension, diabetes, previous stroke, or heart failure

Exclusion criteria:

  • Prior history of AF (past or current), pacemaker, oral anticoagulation (OAC), or contraindication to OAC

Other salient features/characteristics:

  • Prior stroke: 17.6%, prior transient ischemic attack: 10.4%
  • Diabetes mellitus: 28.4%
  • Heart failure: 4.5%
  • Hypertension: 91%
  • CHA2DS2-VASc score: 4
  • Beta-blocker use: 25%, antiplatelet use: 48%

Principal Findings:

The primary outcome, stroke or systemic embolism, for ILR vs. control, was 4.5% vs. 5.6% (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.61-1.05, p = 0.11).

Secondary outcomes for ILR vs. control:

  • AF: 31.8% vs. 12.2% (p < 0.0001)
  • OAC: 29.7% vs. 13.1% (p < 0.0001)
  • Stroke, systemic embolism, or cardiovascular mortality: 6.9% vs. 8.3% (p = 0.1)
  • All-cause mortality: 11.2% vs. 11.3% (p = 1.0)
  • Major bleeding: 4.3% vs. 3.5% (p = 0.11)

Adjudicated stroke for ILR vs. control was: 4.4% vs. 5.5% (p > 0.05); ischemic stroke: 3.7% vs. 4.8% (p = 0.07). Median modified Rankin Scale (mRS) score was 2 in both arms.

Effect of N-terminal pro-B-type natriuretic peptide (NT-proBNP): The median NT-proBNP level was 15 pmol/L (corresponding to 125 pg/mL). NT-proBNP above median was associated with an increased risk of AF diagnosis both in the ILR group (HR 1.84 [95% CI 1.51–2.25]) and the control group (HR 2.79 [95% CI 2.30–3.40]). Participants with NT-proBNP above the median were also at higher risk of clinical events compared with those having lower levels (HR 1.21 [95% CI 0.96–1.54] for stroke or systemic embolism [SE], 1.60 [95% CI, 1.32–1.95] for stroke/SE/cardiovascular death, and 1.91 [95% CI, 1.61–2.26] for all-cause death). Compared with usual care, ILR screening was associated with significant reductions in stroke/SE and stroke/SE/cardiovascular death among participants with NT-proBNP above median (HR 0.60 [95% CI, 0.40–0.90], p for interaction = 0.03 and 0.70 [95% CI, 0.53–0.94], p for interaction = 0.045).

Interpretation:

The results of this trial indicate that continuous monitoring for AF with an ILR (followed by treatment with OAC if AF was detected) was not superior to usual care in reducing stroke or systemic embolism among patients at high risk of stroke but without a known prior history of AF. On post hoc analysis, a benefit was noted among patients with high NT-proBNP at baseline. These findings are hypothesis generating and deserve further investigation. Similar to other trials that focused on screening, this trial found a significantly higher rate of AF with active screening. Further, the use of OAC was appropriately higher in this arm too. However, an effect on clinical outcomes was not observed. Bleeding rates were also not statistically different.

This is an important trial given the recent interest in wearables and other devices for AF screening. Although AF detection was at an expected rate (nearly 30% had occult AF in the ILR arm), the reduction in stroke/systemic embolism rates were lower than expected despite appropriate OAC. It is thus possible that short-duration subclinical AF has less of a clinical impact compared with longer duration and/or clinically significant AF. This could also have resulted in a type II error in this trial. Even if a larger trial shows a benefit in stroke/systemic embolism, it is likely that the number needed to treat for screening would be quite high, and would need to be balanced with a higher bleeding risk in this elderly population. In addition, no benefit in cardiovascular or all-cause mortality was observed.

References:

Xing LY, Diederichsen SZ, Højberg S, et al. Effects of Atrial Fibrillation Screening According to N-Terminal Pro-B-Type Natriuretic Peptide: A Secondary Analysis of the Randomized LOOP Study. Circulation 2023;147:1788-97.

Diederichsen SZ, Frederiksen KS, Xing LY, et al. Severity and Etiology of Incident Stroke in Patients Screened for Atrial Fibrillation vs Usual Care and the Impact of Prior Stroke: A Post Hoc Analysis of the LOOP Randomized Clinical Trial. JAMA Neurol 2022;79:997-1004.

Presented by Dr. Søren Zöga Diederichsen at the European Society of Cardiology Congress (ESC 2022), Barcelona, Spain, August 29, 2022.

Svendsen JH, Diederichsen SZ, Højberg S, et al. Implantable loop recorder detection of atrial fibrillation to prevent stroke (The LOOP Study): a randomized controlled trial. Lancet 2021;398:1507-16.

Editorial Comment: Lowres N, Freedman B. Population screening for atrial fibrillation to prevent stroke. Lancet 2021;398:1463-5.

Presented by Dr. Jesper Hastrup Svendsen at the European Society of Cardiology Virtual Congress, August 29, 2021.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Hypertension

Keywords: ESC Congress, ESC22, ESC21, Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Diabetes Mellitus, Diagnostic Tests, Routine, Electrocardiography, Ambulatory, Embolism, Geriatrics, Heart Failure, Hemorrhage, Hypertension, Natriuretic Peptide, Brain, Primary Prevention, Stroke, Vascular Diseases


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