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

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

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: 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

• Study Type: Observational
• Enrollment (Actual): 34244

Contacts and Locations

Study Locations

• United States
  • California
    • San Mateo, California, United States, 94401
      • Evidation Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

The study population includes an older age group in whom the risk of developing Atrial Fibrillation (AF) is increased and who may benefit from a broad, health-focused Engagement Program paired with the irregular rhythm notification (IRN) alert (photoplethysmogram [PPG] sensor based) and electrocardiogram (ECG) sensor of the Apple Watch Series 5 or later.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Non- Atrial Fibrillation (AF) Cohort; 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; 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.
Atrial Fibrillation (AF) Cohort; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Janssen Scientific Affairs, LLC
• Collaborators: Apple Inc.
• Investigators: Study Director: Janssen Scientific Affairs, LLC Clinical Trial, Janssen Scientific Affairs, LLC

Publications and helpful links

General Publications

• Nikolovski J, Koldijk M, Weverling GJ, Spertus J, Turakhia M, Saxon L, Gibson M, Whang J, Sarich T, Zambon R, Ezeanochie N, Turgiss J, Jones R, Stoddard J, Burton P, Navar AM. Factors indicating intention to vaccinate with a COVID-19 vaccine among older U.S. adults. PLoS One. 2021 May 24;16(5):e0251963. doi: 10.1371/journal.pone.0251963. eCollection 2021.

Helpful Links

• Study website

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2020
• Primary Completion (Actual): January 23, 2025
• Study Completion (Actual): January 23, 2025

Study Registration Dates

• First Submitted: February 18, 2020
• First Submitted That Met QC Criteria: February 18, 2020
• First Posted (Actual): February 19, 2020

Study Record Updates

• Last Update Posted (Actual): July 18, 2025
• Last Update Submitted That Met QC Criteria: July 17, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: CR108633; NOPRODAFL0002 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No