Early rhythm control reduced the primary composite outcome compared with usual care (HR 0.67; 95% CI 0.53-0.84; P<0.001), and its efficacy did not interact with genetic risk for AF or stroke.
RCT (n=1,567)
Randomized
Does early rhythm control reduce cardiovascular events in patients with recently diagnosed atrial fibrillation regardless of genetic predisposition to AF and stroke?
Early rhythm control effectively reduces cardiovascular events in patients with recently diagnosed atrial fibrillation irrespective of their genetic risk for AF or stroke.
Effect estimate: HR 0.67 (95% CI 0.53-0.84)
p-value: p=<0.001
AIMS: The randomized Early Treatment of Atrial Fibrillation for Stroke Prevention Trial found that early rhythm control reduces cardiovascular events in patients with recently diagnosed atrial fibrillation (AF) compared with usual care. How genetic predisposition to AF and stroke interacts with early rhythm-control therapy is not known. METHODS AND RESULTS: 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: Early rhythm control is effective across the spectrum of genetic AF and stroke risk. The association between genetic stroke risk and heart failure calls for research to understand the interactions between polygenic risk and treatment. REGISTRATION: ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org.
Kany et al. (Fri,) conducted a rct in Recently diagnosed atrial fibrillation (n=1,567). Early rhythm control vs. Usual care was evaluated on Composite of cardiovascular death, stroke, and hospitalization for acute coronary syndrome or worsening heart failure (HR 0.67, 95% CI 0.53-0.84, p=<0.001). Early rhythm control reduced the primary composite outcome compared with usual care (HR 0.67; 95% CI 0.53-0.84; P<0.001), and its efficacy did not interact with genetic risk for AF or stroke.