Atrial Fibrillation, Diabetes, Hypertension, Stroke
Conditions
Keywords
atrial fibrillation, cardiac arrhythmia, stroke, implantable loop recorder, bleeding, anticoagulation, hypertension, diabetes, heart failure, mortality
Brief summary
The LOOP study aims to determine whether screening for atrial fibrillation (AF) with implantable loop recorder and initiation of oral anticoagulation (OAC) if AF is detected will reduce the risk of stroke and systemic arterial embolism in patients with risk factors for stroke.
Detailed description
Background: Ischemic stroke is an increasing health problem world-wide (Heidenreich PA, et al. Circulation 2011; PMID 21262990). At least 20% of ischemic strokes are attributable to atrial fibrillation (AF) (Marini C, et al. Stroke J Cereb Circ 2005; PMID 15879330). Another 30% are so-called cryptogenic, possibly related to undiagnosed AF (Brachmann J, et al. Circ Arrhythm Electrophysiol 2015; PMID 26763225). In approximately 30% of a general population of pacemaker or cardioverter defibrillator patients, previously unknown AF will be detected during the first 2-3 years after implantation (Healey JS, et al. N Engl J Med 2012; PMID 22236222; ASSERT). Although the majority of these AF episodes are short-lasting and asymptomatic, the ASSERT study found that such AF is associated with risk of stroke. Since this was published, screening for AF has received intensified attention by researchers and the industry, although available evidence does not yet support systematic mass screening. \- Aims: The LOOP study will determine whether long-term continuous screening and initiation of OAC for AF episodes lasting ≥6 minutes will reduce the risk of stroke in patients with stroke risk factors. \- Methods: Patients from the general population will receive a letter of invitation from one of four study centers located in 3 of Denmark's 5 administrative regions. Eligible study participants must be ≥70 years old and have ≥1 of the following stroke risk factors; hypertension, diabetes, heart failure or previous stroke, while any history of AF or existing cardiac implantable electronic device are exclusion criteria. A total of 6000 participants will be randomized 3:1 to control (n=4500) or to receive an implantable loop recorder with continuous remote monitoring (n=1500) and initiation of OAC if AF is detected. The primary endpoint is time to first stroke or systemic arterial embolism. The trial is event-driven and planned to continue until 279 adjudicated primary events have occurred. Sub-studies include AF characterization, health economic analyses, quality-of-life assessments, cognitive function assessments, and studies of risk markers from 12-lead ECG, genetics, cardiac and brain imaging, biochemistry, and more.
Interventions
DEVICEImplantable loop recorder (Medtronic Reveal LINQ(TM))
The patients in the experimental arm receive an implantable loop recorder (Medtronic Reveal LINQ(TM)) with continuous monitoring, and are followed by daily automated remote transmissions. New arrhythmia episodes are reviewed daily by an experienced medical doctor. If AF lasting ≥6 minutes is detected and confirmed by at least two senior cardiologists, OAC is initiated. Decision about specific type of OAC, and possible further clinical work-up or treatment, is left to the treating physician and the patient. The remote monitoring continues until end of service of the device, patient withdrawal or other end-of-study.
Sponsors
Bispebjerg Hospital
Zealand University Hospital
Odense University Hospital
University of Southern Denmark
Aalborg University
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
70 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Age 70-90 years, and * Previously diagnosed with ≥1 of: * Diabetes mellitus (type 1 or type 2, with or without medical therapy) * Hypertension (with or without medical therapy) * Heart failure * Previous diagnosed stroke (previous transient ischemic attack is not considered an inclusion criterion)
Exclusion criteria
* History of atrial fibrillation or flutter irrespective of type * Cardiac pacemaker or defibrillator (with or without re-synchronization therapy) * Contraindication to oral anticoagulation therapy * Anticoagulation therapy; vitamin K antagonists, direct oral anticoagulants, or (low-molecular) heparins. Therapy with platelet inhibitors such as acetyl-salicylic acid, clopidogrel, persantine is not considered an exclusion criterion * Renal failure treated with permanent dialysis * Uncorrected congenital heart disease, or severe valvular stenosis, obstructive cardiomyopathy, active myocarditis, or constrictive pericarditis. * On a waiting list for major surgery (cardiac, thoracic or abdominal) * Cardiac or thoracic surgery has been performed within 3 months from inclusion * Any major organ transplant (e.g. lung, liver, heart, or kidney) * Cytotoxic or cytostatic chemotherapy and/or radiation therapy for treatment of a malignancy within 6 months before randomization or clinical evidence of current malignancy with the following exceptions: Basal or squamous cell carcinoma of the skin, cervical intraepithelial neoplasia, prostate cancer (if stable, localized disease with a life expectancy of \> 2.5 years in the opinion of the investigator) * Life-expectancy shorter than 6 months * Known to be human immunodeficiency virus (HIV) positive with an expected survival of less than 5 years due to HIV infection * Recent (within 3 months) history of alcohol or drug abuse based on self-reporting * Any condition (e.g. psychiatric illness, dementia) or situation, that in the investigators opinion could put the subject at significant risk, confound the study results, or interfere significantly with the subject participation in the study * Unwillingness to participate or patient does not understand Danish language
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to adjudicated stroke or systemic arterial embolism | At the completion of the event-driven trial, expected 4 years | Time to the first of one of the components of the combined primary endpoint * adjudicated stroke, or * adjudicated systemic arterial embolism |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to adjudicated ischemic stroke/transient ischemic attack/systemic arterial embolism | At the completion of the event-driven trial, expected 4 years | Time to the first of one of the components of the combined endpoint * adjudicated ischemic stroke, or * adjudicated transient ischemic attack, or * adjudicated systemic arterial embolism |
| Time to adjudicated stroke, or systemic arterial embolism, or cardiovascular death | At the completion of the event-driven trial, expected 4 years | Time to the first of one of the components of the combined endpoint * adjudicated stroke, or * adjudicated systemic arterial embolism, or * adjudicated cardiovascular death |
| Time to adjudicated cardiovascular death | At the completion of the event-driven trial, expected 4 years | — |
| Time to death by any cause | At the completion of the event-driven trial, expected 4 years | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Presence of complications related to loop recorder implantation; infection, hematoma, or other complication related to device implantation requiring intervention | During implantable loop recorder monitoring, expected 3 years | — |
| Time to diagnosis of AF | At the completion of the event-driven trial, expected 4 years | — |
| Change from baseline in quality of life | 3 years (from baseline to the at the fourth study visit) | Quality of life assessed with the EuroQol, 5 Dimensions with 5 Levels instrument (EQ-5D-5L) with range 5-25 and higher values indicating higher quality of life. |
| Time to initiation of OAC | At the completion of the event-driven trial, expected 4 years | — |
| Time to adjudicated intracranial hemorrhage not classified as stroke | At the completion of the event-driven trial, expected 4 years | — |
| Time to adjudicated hemorrhagic stroke | At the completion of the event-driven trial, expected 4 years | — |
| Time to major bleeding as defined by the International Society on Thrombosis and Haemostasis criteria | At the completion of the event-driven trial, expected 4 years | — |
Countries
Denmark
Outcome results
None listed