Array genotyping and imputation for common genetic variants were performed.
Polygenic risk scores (PRS) were calculated for AF (PRS-AF) and
ischaemic stroke risk (PRS-
stroke). The effects of PRS-AF and PRS-
stroke on the primary outcome (composite of cardiovascular death,
stroke, and hospitalization for
acute coronary syndrome or worsening
heart failure), its components, and recurrent AF were determined.A total of 1567 of the 2789 trial patients were analysed [793 randomized to early rhythm control; 774 to usual care, median age 71 years (65-75), 704 (44%) women]. Baseline characteristics were similar between randomized groups. Early rhythm control reduced the primary outcome compared with usual care [HR 0.67, 95% CI: (0.53, 0.84), P < 0.001]. The randomized intervention, early rhythm control, did not interact with PRS-AF (interaction P = 0.806) or PRS-
stroke (interaction P = 0.765). PRS-AF was associated with recurrent AF [HR 1.08 (01.0, 1.16), P = 0.047]. PRS-
stroke showed an association with the primary outcome [HR 1.13 (1.0, 1.27), P = 0.048], driven by more
heart failure events [HR 1.23 (1.05-1.43), P = 0.010] without differences in
stroke [HR 1.0 (0.75, 1.34), P = 0.973] in this well-anticoagulated cohort. In a replication analysis, PRS-
stroke was associated with incident AF [HR 1.16 (1.14, 1.67), P < 0.001] and with incident
heart failure in the UK Biobank [HR 1.08 (1.06, 1.10), P < 0.001]. The association with
heart failure was weakened when excluding AF patients [HR 1.03 (1.01, 1.05), P = 0.001].
CONCLUSIONS: ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org.