PER DIEM
(2021)Objective
To determine whether 12 months of implantable loop recorder monitoring detects more atrial fibrillation compared with conventional external loop recorder monitoring for 30 days in patients with a recent ischemic stroke
Study Summary
• Most AF detected after 30 days—only 4.7% ILR vs 3.3% ELR at 30 days, but 10.7% vs 1.3% between 30 days and 12 months
• All patients with detected AF were started on oral anticoagulation
Intervention
Implantable loop recorder (Reveal LINQ) for 12 months vs External loop recorder (SpiderFlash-t) for 30 days
Inclusion Criteria
Adults ≥18 years with ischemic stroke confirmed by neuroimaging within 6 months, without known AF or prior extended (>7 days) external ECG monitoring
Study Design
Arms: Implantable loop recorder (ILR) group vs External loop recorder (ELR) group
Patients per Arm: ILR: 150, ELR: 150
Outcome
• AF at 30 days: 4.7% ILR vs 3.3% ELR (NS)
• AF 30 days to 12 months: 10.7% ILR vs 1.3% ELR (RR 8.0, P=0.001)
Bottom Line
Implantable loop recorder monitoring for 12 months detected significantly more AF than 30-day external loop recorder monitoring (15.3% vs 4.7%, RR 3.29). The difference emerged primarily after 30 days of monitoring. All patients with newly diagnosed AF were started on oral anticoagulation therapy.
Major Points
- At 12 months, AF was detected in 15.3% of ILR patients vs 4.7% of ELR patients (RR 3.29, 95% CI 1.45-7.42, P=0.003)
- At 30 days, AF detection was similar: 4.7% ILR vs 3.3% ELR (between-group difference 1.3%, P=0.77)
- Between 30 days and 12 months, significantly more AF was detected: 10.7% ILR vs 1.3% ELR (RR 8.0, P=0.001)
- 100% of patients with newly diagnosed definite AF were started on oral anticoagulation
- 66.3% of patients had stroke of undetermined etiology; 16% had small vessel occlusion
- Detection rate with ILR (15.3%) was comparable to CRYSTAL-AF (12.4%) despite including all stroke subtypes
- ELR detection rate (3.3% at 30 days) was lower than EMBRACE trial (16.1%) due to more rigorous AF definition (≥2 min)
- Older age was the strongest predictor of AF detection (RR 1.03 per year); patients >80 years had ~50% AF rate
- NNT with ILR vs ELR to detect one AF case = 10 patients
Study Design
- Study Type
- Investigator-initiated, open-label, randomized clinical trial
- Randomization
- Yes
- Blinding
- Open-label for patients and investigators; outcome adjudication by 2 cardiac electrophysiologists blinded to all clinical data
- Sample Size
- 300
- Follow-up
- 12 months (final follow-up December 2018)
- Centers
- 3
- Countries
- Canada
Primary Outcome
Definition: Development of definite AF or highly probable AF (adjudicated new AF lasting ≥2 minutes within 12 months of randomization). Definite/highly probable AF defined as good quality recording showing continuously irregular QRS complexes for >2 minutes with no visible P waves or clearly identified fibrillatory atrial activity/flutter waves.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 4.7% (7/150 patients) | 15.3% (23/150 patients) | 3.36 (1.44 to 7.84 (adjusted for age and sex)) | 0.003 |
Limitations & Criticisms
- Open-label design for patients and investigators, though outcome adjudication was blinded
- Median 2-month delay between stroke onset and enrollment may have decreased AF detection slightly
- Variable pre-enrollment investigations; not all patients had echocardiography or 24-hour Holter before enrollment
- AF definition required ≥2 minutes duration due to ILR technical limitations, which may miss shorter clinically relevant episodes
- 8.6% of participants did not complete prescribed monitoring, potentially underestimating true AF rates
- Phone assessments did not use validated questionnaire for stroke/TIA events
- Study not powered to detect differences in clinical outcomes (stroke, death)
- Included all stroke subtypes, not just cryptogenic, limiting direct comparison with CRYSTAL-AF
- Cost-effectiveness analysis not performed
- Single-country study (Canada) may limit generalizability
Citation
JAMA. 2021;325(21):2160-2168