A Study to Investigate if Early Atrial Fibrillation (AF) Diagnosis Reduces Risk of Events Like Stroke in the Real-World

Study Overview
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Brief Summary
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The primary objectives of this study are to identify and diagnose Atrial Fibrillation (AF), evaluate improvement in cardiovascular (CV) outcomes, improve direct oral anti-coagulant (DOAC) adherence and persistence, and better characterize participants and identify predictors of disease.

Official Title
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HEARTLINE - A Heart Health Study Using Digital Technology to Investigate if Early AF Diagnosis Reduces the Risk of Thromboembolic Events Like Stroke IN the Real-world Environment

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Device: Heart healthy Engagement Program with the Apple Watch Series 5 or later
* Device: Anti-Coagulation Adherence Module with the Apple Watch Series 5 or later


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Medicare beneficiary either with Original or Medicare advantage Authorize electronic access to their healthcare claims data Authorize sharing of device sensor, health, and Heartline app data from their iPhone and Apple Watch (if applicable). This includes Apple Watch and iPhone sensor data that is not publicly available Willing and able to provide informed consent by electronically signing the remote e-consent directly in the Heartline app prior to any study-related activities. Electronically signing the remote e-consent indicates that he/she understands the purpose of, and activities required for the study and is willing to participate for the 2-year Active Engagement Phase, with continued passive collection of their device and healthcare claims data for an additional 1 year in the Post-Engagement Follow-Up Phase Current resident of the US at the time of eligibility screening, defined by self-reported state of residence within the 50 states or the US or District of Columbia Own an iPhone 6s or later with iOS Version 12.2 or later Exclusion Criteria: Limited life expectancy and/or current diagnosis of terminal cancer Unable to confirm meeting inclusion criteria, including ability to consent and participate in human participant's research Own an Apple Watch Series 0 paired with an iPhone at the time of screening eligibility (these participants are not eligible for any study cohorts [randomized or observational]) Have a confirmed diagnosis of Atrial Fibrillation (AF) at study entry and currently taking a direct oral anti-coagulant (DOAC) for less than (<) 30 days, currently taking other anti-coagulant medication(s) for AF other than a DOAC, or currently not taking medication for AF

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Non- Atrial Fibrillation (AF) Cohort<br>Participants without a history of AF will be randomly assigned into the study to either an Apple Watch/iPhone group or an iPhone group only. | Device: Heart healthy Engagement Program with the Apple Watch Series 5 or later<br>* No drug will be given as part of this study. Participants without a diagnosis of AF will be enrolled and a heart healthy Engagement Program delivered via the Heartline app on the iPhone with the Apple Watch Series 5 or later.<br>|
| Atrial Fibrillation (AF) Cohort<br>Participants with a diagnosis of AF taking a direct oral anti-coagulant (DOAC) for at least 30 days will be randomly assigned to Apple Watch/iPhone group or iPhone group only. | Device: Anti-Coagulation Adherence Module with the Apple Watch Series 5 or later<br>* No drug will be given as part of this study. Participants with a diagnosis of AF (taking a DOAC for at least 30 days) will be enrolled and an Anti-Coagulation Adherence Module delivered via the Heartline app on the iPhone with an Apple Watch Series 5 or later.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from Randomization to Clinical Diagnosis of Atrial Fibrillation (AF) | Time to a clinical diagnosis of AF obtained from healthcare claims database. | Up to 3 years | 
| Percent Days Covered (PDC) by Direct Oral Anti-Coagulant (DOAC) Prescription Fills | Percent days of covered prescription DOAC use minus any evidence of no prescription use/refills over the time interval chosen. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Composite of 6-component Events (Ischemic Stroke/TIA, MI, Non-CNS Embolism or Thrombosis, Hospitalization or ED Visit for HF, CV Hospitalization and ACM) | Time to composite of 6-component events (ischemic stroke/transient ischemic attack [TIA], myocardial infarction [MI], non-central nervous system [CNS] embolism or thrombosis, hospitalization or emergency department [ED] visit due to heart failure [HF], cardiovascular [CV] hospitalization, and all-cause mortality [ACM]), obtained from randomization in the healthcare claims database, will be reported. | Up to 3 years | 
| Summary of Total Cost of Care Delivery, Total Health Resource Utilization (HRU), and Cost Effectiveness | Summary of total cost of care delivery, total HRU, and cost effectiveness will be reported. Total costs of care reported as number of HRU events times the unit cost for each event. HRU reported as counts of HRU events. Cost effectiveness to be assessed by including the cost to diagnosis, treatment and reported clinical outcome. | Up to 3 years | 
| Time to Ischemic stroke/TIA | Ischemic stroke/TIA is defined as a hospitalization/diagnosis for Ischemic stroke/TIA. | Up to 3 years | 
| Time to MI | MI is defined as a hospitalization/diagnosis for MI. | Up to 3 years | 
| Time to non-CNS Embolism or Thrombosis | Non-CNS embolism or thrombosis is defined as hospitalization for non-CNS thromboembolic events. | Up to 3 years | 
| Time to Hospitalization or ED for HF | Hospitalization or ED visit for HF is defined as an in-patient stay or an outpatient ED visit for HF. | Up to 3 years | 
| Time to CV Hospitalization | Hospitalization for CV is defined as an in-patient stay for CV disease. | Up to 3 years | 
| Time to all-Cause Mortality | All-cause mortality (ACM) is defined as deaths from all (reported) causes. | Up to 3 years | 
| Time to Composite Bleeding Events Resulting in Hospitalization | Hospitalization for composite bleeding events (such as intracranial hemorrhage, gastrointestinal [GI], respiratory, intraocular) is defined as in-patient stay for bleeding events, as reported in the healthcare claims database. | Up to 3 years | 
| Time to Hospitalization for Hemorrhagic Stroke | Hospitalization for hemorrhagic stroke is defined as an in-patient stay for a hemorrhagic stroke. | Up to 3 years |