Interactions of blood biomolecules with early rhythm control in atrial fibrillation patients: exploratory analysis of the EAST-AFNET 4 biomolecule study

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AIMS: Early rhythm control reduces cardiovascular events in patients with atrial fibrillation (AF) and cardiovascular comorbidities. Whether this effect is consistent across severities of different AF-associated conditions is not known. METHODS: In the EAST-AFNET 4 biomolecule study (n = 1586; median age 70 years; 45% women), 14 circulating biomarkers reflecting inflammation, fibrosis, ageing, cardiac strain, and myocardial damage were quantified. Log-transformed, winsorized biomarkers were analysed in quintiles to detect non-linear associations and as continuous parameters. Cox proportional hazards models evaluated associations with the primary outcome (cardiovascular death, stroke, or unplanned hospitalization for heart failure or acute coronary syndrome) and the safety outcome (death, stroke, or major bleeding) of the trial, including interaction terms for biomarkers and randomized treatment [early rhythm control (ERC) vs. usual care (UC)]. Two independent cohorts, BBC-AF resembling UC and a TRUST snapshot resembling ERC were combined for external replication. All tests were exploratory. RESULTS: ERC reduced the primary outcome consistently across biomarker concentrations. No signal for treatment interaction was observed for 13 of 14 biomarkers for the primary outcome. For BMP10, a nominal interaction was observed in categorical analyses, suggesting an attenuated treatment effect of ERC in patients in the lowest BMP10 quintile. No interaction was detected for continuous parameters. Similar patterns were observed in exploratory analyses of the replication cohort. CONCLUSION: ERC therapy is effective across patients with different severities of conditions associated with AF as quantified by biomolecule concentrations. A potentially attenuated effect of ERC with low BMP10 concentrations warrants further research.This analysis is part of the EAST-AFNET 4 trial biomolecule study, the original trial has been registered under the official title: Early Therapy of Atrial Fibrillation for Stroke Prevention Trial (EAST) (EudraCT 2010-021258-20) at https://clinicaltrials.gov/study/NCT01288352.

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