CClinicalTrials.gg
CompletedNCT04276441Updated Jul 18, 2025

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

An observational study in Atrial Fibrillation, sponsored by Janssen Scientific Affairs, LLC. Completed at 1 site in United States. Open to participants aged 65 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-07-18.

Sponsored by Janssen Scientific Affairs, LLC · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
34,244
Ages
65 Years and older
Sex
All
01

Study summary

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.

02

Conditions studied

  • Atrial Fibrillation

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03

Who can participate

Ages eligible
65 Years and older
Sexes eligible
All
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.

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

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
04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
34,244 participants (actual)
Patient registry
No

Groups and cohorts

  • 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

  • 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

Interventions

  • DeviceHeart 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.

  • DeviceAnti-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.

05

What researchers measure

Primary outcomes

  1. Time from Randomization to Clinical Diagnosis of Atrial Fibrillation (AF)

    Time to a clinical diagnosis of AF obtained from healthcare claims database.

    Time frame: Up to 3 years

  2. 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.

    Time frame: Up to 3 years

Secondary outcomes

  1. 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.

    Time frame: Up to 3 years

  2. 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.

    Time frame: Up to 3 years

  3. Time to Ischemic stroke/TIA

    Ischemic stroke/TIA is defined as a hospitalization/diagnosis for Ischemic stroke/TIA.

    Time frame: Up to 3 years

  4. Time to MI

    MI is defined as a hospitalization/diagnosis for MI.

    Time frame: Up to 3 years

  5. Time to non-CNS Embolism or Thrombosis

    Non-CNS embolism or thrombosis is defined as hospitalization for non-CNS thromboembolic events.

    Time frame: Up to 3 years

  6. 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.

    Time frame: Up to 3 years

  7. Time to CV Hospitalization

    Hospitalization for CV is defined as an in-patient stay for CV disease.

    Time frame: Up to 3 years

  8. Time to all-Cause Mortality

    All-cause mortality (ACM) is defined as deaths from all (reported) causes.

    Time frame: Up to 3 years

  9. 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.

    Time frame: Up to 3 years

  10. Time to Hospitalization for Hemorrhagic Stroke

    Hospitalization for hemorrhagic stroke is defined as an in-patient stay for a hemorrhagic stroke.

    Time frame: Up to 3 years

06

Study locations

1 site
  • Evidation Health
    San Mateo, California 94401, United States
07

References and documents

Publications

  • Hills MT, Korjian S, Chi G, Natale A, Saxon L, Ferdinand KC, Kwaku KF, Brancato S, Hughes A, Baca-Motes K, Steinhubl SR, Wessler J, Goldberg N, Asthana A, Shute K, Applebaum J, Doran K, Nikolovski J, Kaul S, Wentworth D, Damaraju CV, Tavakoli C, Patel M, Curtis AB, Spertus JA, Gibson CM; Heartline Executive Committee and Steering Committee. Direct-to-Participant Enrollment in a Virtual Trial: Lessons Learned From the Heartline Study. JACC Adv. 2026 Apr;5(4):102662. doi: 10.1016/j.jacadv.2026.102662. Epub 2026 Mar 23. PubMed 41875816 ↗
  • Nikolovski J, Navar AM, Steinhubl S, Baca-Motes K, Curtis AB, Peterson ED, Lakkireddy D, Tarino M, Juan S, Damaraju CRV, Wentworth D, Wildenhaus K, Patel M, Tavakoli C, Gibson CM, Spertus JA; Heartline Steering Committee. The Heartline Experience: Achieving Long-Term Participant Engagement in Digital Health Technology Trials. JACC Adv. 2025 Sep;4(9):102072. doi: 10.1016/j.jacadv.2025.102072. Epub 2025 Aug 20. PubMed 40839901 ↗
  • Grine M, Guerreiro C, Moscoso Costa F, Nobre Menezes M, Ladeiras-Lopes R, Ferreira D, Oliveira-Santos M. Digital health in cardiovascular medicine: An overview of key applications and clinical impact by the Portuguese Society of Cardiology Study Group on Digital Health. Rev Port Cardiol. 2025 Feb;44(2):107-119. doi: 10.1016/j.repc.2024.08.009. Epub 2024 Oct 10. English, Portuguese. PubMed 39393635 ↗
  • Gibson CM, Steinhubl S, Lakkireddy D, Turakhia MP, Passman R, Jones WS, Bunch TJ, Curtis AB, Peterson ED, Ruskin J, Saxon L, Tarino M, Tarakji KG, Marrouche N, Patel M, Harxhi A, Kaul S, Nikolovski J, Juan S, Wildenhaus K, Damaraju CV, Spertus JA; Heartline Steering Committee. Does early detection of atrial fibrillation reduce the risk of thromboembolic events? Rationale and design of the Heartline study. Am Heart J. 2023 May;259:30-41. doi: 10.1016/j.ahj.2023.01.004. Epub 2023 Jan 12. PubMed 36642226 ↗
  • 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. PubMed 34029345 ↗
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Registry details

Key details

Study ID
NCT04276441
Lead sponsor
Janssen Scientific Affairs, LLC
Collaborators
Apple Inc.
Responsible party
Sponsor
First posted
Feb 19, 2020
Start date
Feb 25, 2020
Primary completion
Jan 23, 2025
Completion
Jan 23, 2025
Last update
Jul 18, 2025

Study contacts

Janssen Scientific Affairs, LLC Clinical Trial
study director · Janssen Scientific Affairs, LLC

Oversight

Data monitoring committee
Yes
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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