Background: 
eBRAVE-AF was a siteless, randomized, controlled trial that showed that digital smart-device based screening for atrial fibrillation (AF) significantly increased the detection rate of treatment-relevant AF when compared to usual care. In this pre-specified subgroup analysis we aimed to investigate the effect of age on compliance, efficacy of digital screening, as well as the interaction between age and AF-triggered major adverse cardiovascular complications (MACCE). 

Methods: 

5.551 individuals, free of AF at baseline were randomized using simple randomization to digital screening (n=2.860) or usual care (n=2.691). For digital screening, participants used a certified app to screen for irregularities in their pulse waves by means of photoplethesmography (PPG), and abnormal findings were confirmed by a 14-day Holter-ECG. The primary endpoint was newly diagnosed AF treated with oral anticoagulation (OAC) within 6 months. After 6 months, participants were invited to cross-over for a second study phase with reverse assignment. For this analysis we combined the two phases of the study using multilevel clustered Cox-regression analysis.  Age was dichotomized at the pre-specified cut-off value of ≥/< 65 years.

Results: 

The median age of the cohort was 65 (IQR 11) years, the median CHA₂DS₂-VASc score was 3 (IQR 1), 31% participants were females. During the study, 300.509 PPG-measurements were performed, corresponding to a median of 53 (IQR 62) per active participant. Age ≥ 65 years was associated with a better compliance in terms of more frequent PPG-measurements (55± 63) compared to age < 65 years (50±59 measurements; p = 0.003). During a median follow-up time of 12 months 102 subjects reached the primary endpoint (including 2 endpoints in the cross-over window).  Age ≥ 65 (N = 3.028; 81 events) compared to age < 65 years (N = 2.523; 21 events) was a significant predictor for reaching the primary endpoint in participants assigned to both digital screening (HR 3.64; 95% CI 2.03–6.53; p <0.001) and usual-care (HR 2.55; 95% CI 1.09 – 5.97; p = 0.031) groups. There was no significant interaction (p = 0.497) between age and the efficacy of digital screening for reaching the primary endpoint (Fig. 1). While digital screening significantly increased the detection rate of AF requiring OAC in subjects aged ≥ 65 (HR 2.55; 95% CI 1.56–4.15; p < 0.001) in participants aged < 65 years this effect did not reach the level of statistical significance (HR 1.78; 95% CI 0.72 – 4.43; p = 0.214), most probably due to the lower event-rate in this age group. Although the incidence of AF in participants aged < 65 years was much lower compared to subjects aged ≥ 65 years (1.5% vs. 3.2%; p < 0.001), AF in participants aged < 65 years was associated with higher risk for developing MACCE (HR 14.72; 95% CI 6.40–33.85; p < 0.001) compared to participants aged ≥ 65 years (HR 3.56; 95% CI 1.39–9.15; p = 0.008; p-interaction = 0.026; Fig. 2).

Conclusion:

In a large-scale clinical trial, comparing digital screening to usual care for detecting AF requiring OAC, age ≥ 65 years was associated with better compliance to the study protocol and higher-risk for developing AF requiring OAC. There was no significant interaction between age and the efficacy of digital screening for detecting AF requiring OAC.  In both age groups, AF detection was associated with increased risk for subsequent MACCE. However, this association was significantly stronger among younger patients.