Strengths and limitations
PRS, stroke
STROKE
Collection of analysable biosamples in a large sub-population (69%) of eligible patients randomized in the EAST-AFNET 4 trial and systematic collection of adjudicated outcomes over a 5.1-year follow-up time are strengths of this analysis. Another strength is the continuous delivery of therapy of AF including anticoagulation and treatment of cardiovascular conditions. Both genotyping and imputation for all participants were carried out in the same sequencing centre to avoid systematic bias. Although the sample size contains PRS and outcomes over a mean follow-up duration of 5 years in 1567 patients, the power is too small to detect or rule out weak interactions between PRS and treatment. Information on recurrent AF was not continuously collected in both groups and was included as a time-to-event variable in this analysis. A strength is the use of PRS as continuous risk in addition to quintile groups. The grouping of genetic risk by quintiles is largely arbitrary although common practice in genetic studies. No gold standard PRS for AF or stroke is established and different methods for construction were not compared in this study. Our study focuses on a European sample and did not consider ethnicity in the enrolment of the trial. External validity in cohorts of diverse ethnicities is desirable. The choice of anti-arrhythmic drug therapy can be different depending on the country and catheter ablation was only partly used in this study. Therefore, these findings might not generalize to other cohorts of rhythm control. Due to the explorative design of the study, unadjusted 