Novel risk model for predicting incident atrial fibrillation in patients at high cardiovascular risk receiving omega-3 fatty acid: sub-analysis from the STRENGTH randomized clinical trial

Background Several randomized trials have demonstrated that fish oils are associated with higher risk of incident atrial fibrillation (AF) than placebo, however the risk factors for developing new AF in these patients remain unknown. We analyzed the associated factors and developed a novel risk score for predicting AF in patients at elevated cardiovascular risk receiving ω-3 carboxylic acid (CA) in this sub-analysis of the STRENGTH trial. Methods The STRENGTH trial randomized 13,078 patients at high cardiovascular risk at a 1:1 ratio to receive either ω-3 CA or corn oil placebo at 675 centers from 10/30/2014 to 6/14/2017 . Patients receiving ω-3 CA without history of AF were studied, and stepwise multivariable Cox proportional hazards regression was performed for new AF during follow-up, constructed using baseline demographical, clinical and laboratory parameters. Results Amongst 6,000 patients receiving ω-3 CA without history of AF in the STRENGTH trial, 126 (2.1%) developed AF during mean follow-up of 3.5±0.8 years. Results from the multivariable Cox regression analyses are presented in the Table, from which a novel risk score composed of older age, male sex, higher body mass index, history of heart failure, metformin use and high-sensitivity C-reactive protein was developed. The score (total -1 to 11) had c-index of 0.70 for predicting incident AF in our cohort. Conclusion We developed the first risk score for predicting incident AF in patients taking fish oils, with moderate discriminative ability internally. Further research is necessary to externally validate our risk score and determine how it may guide treatment and prevention of AF and improve clinical outcomes.