Three year clinical outcomes in a nationwide, observational, siteless clinical trial of atrial fibrillation screening-mHealth Screening to Prevent Strokes (mSToPS)

Abstract

Background: Atrial fibrillation (AF) is common, often without symptoms, and is an independent risk factor for mortality, stroke and heart failure. It is unknown if screening asymptomatic individuals for AF can improve clinical outcomes.

Methods: mSToPS was a pragmatic, direct-to-participant trial that randomized individuals from a single US-wide health plan to either immediate or delayed screening using a continuous-recording ECG patch to be worn for two weeks and 2 occasions, ~3 months apart, to potentially detect undiagnosed AF. The 3-year outcomes component of the trial was designed to compare clinical outcomes in the combined cohort of 1718 individuals who underwent monitoring and 3371 matched observational controls. The prespecified primary outcome was the time to first event of the combined endpoint of death, stroke, systemic embolism, or myocardial infarction among individuals with a new AF diagnosis, which was hypothesized to be the same in the two cohorts but was not realized.

Results: Over the 3 years following the initiation of screening (mean follow-up 29 months), AF was newly diagnosed in 11.4% (n = 196) of screened participants versus 7.7% (n = 261) of observational controls (p<0.01). Among the screened cohort with incident AF, one-third were diagnosed through screening. For all individuals whose AF was first diagnosed clinically, a clinical event was common in the 4 weeks surrounding that diagnosis: 6.6% experienced a stroke,10.2% were newly diagnosed with heart failure, 9.2% had a myocardial infarction, and 1.5% systemic emboli. Cumulatively, 42.9% were hospitalized. For those diagnosed via screening, none experienced a stroke, myocardial infarction or systemic emboli in the period surrounding their AF diagnosis, and only 1 person (2.3%) had a new diagnosis of heart failure. Incidence rate of the prespecified combined primary endpoint was 3.6 per 100 person-years among the actively monitored cohort and 4.5 per 100 person-years in the observational controls.

Conclusions: At 3 years, screening for AF was associated with a lower rate of clinical events and improved outcomes relative to a matched cohort, although the influence of earlier diagnosis of AF via screening on this finding is unclear. These observational data, including the high event rate surrounding a new clinical diagnosis of AF, support the need for randomized trials to determine whether screening for AF will yield a meaningful protection from strokes and other clinical events.

Trail registration: The mHealth Screening To Prevent Strokes (mSToPS) Trial is registered on ClinicalTrials.gov with the identifier NCT02506244.

Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: Steve Steinhubl – NIH UL1TR002550 grant support; Qualcomm Foundation. Jill Waalen – No conflicts of interest Anirudh Sanyal - Employee, Healthagen, LLC Alison Edwards – Employee, Healthagen, LLC Lauren Ariniello - NIH UL1TR002550 grant support Gail Ebner - NIH UL1TR002550 grant support; Qualcomm Foundation Katie Baca-Motes - No conflicts of interest Bob Zambon- Employee, Janssen Pharmaceuticals (a subsidiary of Johnson & Johnson); Stockholder Johnson & Johnson. Troy Sarich – Employee, Johnson & Johnson; Stockholder Johnson & Johnson. Eric Topol – NIH UL1TR002550 grant support; Qualcomm Foundation This support does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. CONSORT flow diagram.

Flow of participants beginning with all potentially eligible individuals, those enrolled and then those included in the 4 month, 1-year and 3-year analyses.

Fig 2. Atrial fibrillation diagnosis.

A.) Cumulative Probability of a diagnosis of atrial fibrillation in the 3 years following the initiating of monitoring. B.) Rate of new diagnosis of atrial fibrillation in the monitored and observational cohorts after completion of active monitoring. All new diagnoses occurring annually after 6 months from the initiation of screening.

Fig 3. Primary endpoint.

Cumulative incidence of the combined primary endpoint of death, stroke, systemic emboli or myocardial infarction in actively monitored and observational control cohorts over the 3 years following initiation of screening.

Fig 4. Primary endpoint in those receiving a new diagnosis of atrial fibrillation.

Cumulative incidence of the combined primary endpoint in individuals diagnosed with atrial fibrillation in A.) the actively monitored and observational control cohorts, and B.) the actively monitored cohort based on whether their initial diagnosis of AF was via ECG patch screening or via a clinical diagnosis, and the observational control cohort.

Fig 5. Clinical events surrounding a new atrial fibrillation diagnosis.

Clinical Events in the two weeks preceding and the 2 weeks following a new atrial fibrillation (AF) diagnosis, inclusive of the diagnosis date, in the observational cohort and the actively monitored cohort based on whether their initial diagnosis of AF was via ECG patch screening or via a clinical diagnosis.