Identifying a Heterogeneous Effect of Atrial Fibrillation Screening in Older Adults: A Secondary Analysis of the VITAL-AF Trial.

Background: One-time atrial fibrillation (AF) screening trials have produced mixed results; we sought a subset for whom screening is effective. Methods: We conducted a secondary analysis of VITAL-AF, a randomized trial of one-time, brief, single-lead ECG screening during primary care visits. We tested two approaches to identify a subgroup where screening is effective. First, we developed an effect-based model using a T-learner. Specifically, we separately predicted the likelihood of AF diagnosis under screening and usual care conditions; the difference in probabilities was the predicted screening effectiveness. Second, we used a validated AF risk model to test for heterogeneous screening effectiveness. Results: In the effect-based analysis, in the highest quartile of predicted screening effectiveness, AF diagnosis rates were higher in the screening group (4.00 vs. 2.88 per 100 person-years, rate difference 1.12, 95% CI 0.11 to 2.13). In the risk-based analysis, in the highest quartile of baseline AF risk, AF diagnosis rates were also higher in the screening group (5.55 vs. 4.23 per 100 person-years, rate difference 1.32, 95% CI 0.14 to 2.50). Predicted screening effectiveness and predicted baseline AF risk were weakly correlated (Spearman correlation coefficient 0.23). Patients with low primary care use, using rate control medications, females, and Black patients were overrepresented in the high-effectiveness group even when they were not at high risk of developing AF. Conclusions: In a secondary analysis of VITAL-AF, we identified subgroups where one-time screening was associated with increased AF diagnoses using both effect-based and risk-based approaches. In this study, predicted AF risk was only a partial proxy for predicted screening effectiveness. Even when individuals are not in the high-risk subset, features like low primary care use and rate control medication use can identify individuals for whom AF screening has a large impact. Future AF screening efforts should focus on screening both "high-risk" and "high-effectiveness" individuals. What is Known: Because trials testing office-based screening for atrial fibrillation have produced mixed results, some have suggested we focus screening efforts on high-risk individuals.Newer methods allow us to test for screening heterogeneity using risk-based analyses and separately effect-based analyses, which disentangle screening effects from baseline disease risk. What the Study Adds: Both the risk-based analysis and the effect-based analysis identified "high-risk" and "high-effectiveness" subgroups, respectively, where one-time AF screening was effective."High-risk" and "high-effectiveness" groups only partially overlap; even when individuals are not in the high-risk subset, features like low primary care use and rate control medication use an identify individuals for whom AF screening has a large impact.Future AF screening efforts should focus on screening both "high-risk" and "high-effectiveness" people.