An analysis of 3-year clinical outcomes in a U.S. “digital” clinical trial for atrial fibrillation (AF) screening trial to prevent strokes – the mSToPS study – showed active screening was associated with significantly improved stroke and death rates compared to standard-of-care.
The Scripps Research Translational Institute study data based on mobile health monitoring were presented in a late-breaking science session Monday at the American Heart Association’s (AHA) Scientific Sessions 2020 virtual conference. The study was led by Scripps Translational Science Institute’s Steven Steinhubl, MD, and colleagues.
Although the lifetime risk of AF for adults over the age of 55 is nearly 40%, according to 2018 research published in AHA’s Circulation, routine screening for undiagnosed AF with electrocardiogram (ECG) monitoring is currently not recommended. This is due partly to a lack of data over the impact of screening on clinical outcomes, the researchers noted in their abstract.
However, AF is frequently undiagnosed until a serious clinical event such as stroke or heart failure, they said, adding that AF is an independent risk factor for these issues, as well as for cardiovascular mortality.
Identifying AF through active screening prior to clinical presentation could therefore be a way to improve long-term outcomes in comparison to current standard care, they hypothesized.
The mSToPS study was launched nationwide in the U.S. in 2016. It is a randomized, pragmatic clinical trial of AF that enacted active mobile health monitoring with a wearable ECG sensor patch for a median duration of 24.7 days in the 1,718 enrolled viable participants who were actively monitored. The study ran with a direct-to-participant “siteless” design in Aetna members.
Participants were matched by age, sex and CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, sex category) score with 3,371 viable observational control subjects for the analysis. The mean age at enrollment was 73.7 years, 40.5% of study participants were women, and their median CHA2DS2-VASc baseline was 3.
The predefined outcome at 3 years was time to first event of the combined endpoint of death, stroke, systemic embolism or myocardial infarction as seen via claims and membership data among those with a diagnosis of AF at any time during the trial analysis period. The primary safety endpoint was the incidence rate of hospitalization for a primary bleeding diagnosis.
At the end of the 3-year follow-up period – in which the overall median duration of eligible follow-up was 29 months – 11.4% (196) of those actively monitored were newly diagnosed with AF, compared to 7.7% (261) of observational controls.
The time to first event was significantly lower in the actively monitored cohort, although two-thirds of new diagnoses of AF occurred clinically over the 3 years. In particular, the group had a trend toward a lower rate of the individual endpoint of stroke (2.2 vs 2.6 per 100 person-years, 95% confidence interval [CI], 0.62-1.01; adjusted hazard ratio [HR], 0.79: p=0.06) and a significantly lower rate of death (0.50 vs 0.81 per 100 person-years, 95% CI, 0.37-0.99; adjusted HR 0.61: p=0.047), the researchers noted.
In those with pharmacy data available, anticoagulants were initiated in 45.2% of controls and 44% of the actively monitored cohort.
As for safety, the actively monitored group also saw lower hospitalization rates for bleeding (0.32 vs 0.71 per 100 person-years, 95% CI, 0.26-0.85; adjusted incidence rate ratio (IRR), 0.47: p=0.01), and lower hospitalizations in general at 12.9 vs 18.9 per 100 person-years (95% CI, 0.63-0.76; adjusted IRR, 0.69: p<0.01).
Active screening was associated with a significant improvement in clinical outcomes in the study at 3 years compared with routine care, the researchers noted.
Nevertheless, the authors recognized in the presentation the limitations within the study, including that the comparison between individuals choosing to participate in a randomized trial and an observational cohort may be biased by “unmeasured cofounding.”
They added that endpoints were based on claims data, which limited clinical follow-up to the duration of health plan enrollment, adding that this was less than 3 years for some participants.
Independent replication of the findings is therefore required to be “confident that aggressive pursuit of diagnosing atrial fibrillation in people at high-risk, but without symptoms, is warranted,” according to a presentation slide.
The study was run with Janssen and Aetna as collaborators, according to the study’s ClinicalTrials.Gov record.