Association of body mass index with arrhythmia progression and outcomes in patients with subclinical atrial fibrillation: insights from the ARTESiA trial

Background Overweight and obesity are modifiable risk factors in patients with clinical atrial fibrillation (AF). How body mass index (BMI) relates to arrhythmia progression and outcomes in patients with device-detected subclinical AF (SCAF) is not well defined. Purpose To assess the association of BMI with arrhythmia progression in patients with SCAF, to determine event rates of clinical outcomes across BMI categories, and to explore the potential interaction of BMI with the effects of apixaban vs. aspirin. Methods We performed a secondary analysis of the ARTESiA trial of patients with SCAF <24 hours who were randomized to either apixaban or aspirin. Using regression models adjusted for CHA2DS2-VASc score and randomized treatment, we studied the association of BMI categories (normal: 18.5-24.9 kg/m² [reference], overweight: 25-29.9 kg/m² and obesity: ≥30 kg/m²) with arrhythmia progression (SCAF ≥24 hours or clinical AF) and clinical outcomes. We also formally tested for potential interaction of BMI with the study intervention. Results Of 3,968 patients analyzed, 1,612 (40.6%) had overweight and 1,393 (35.1%) had obesity. During a median of 3.6 years, arrhythmia progression occurred at a rate of 9.2% per year. Compared to patients with normal BMI, progression occurred more frequently in patients who had overweight (adjusted hazard ratio [aHR] 1.17, 95% confidence interval [CI] 1.00-1.37) and obesity (aHR 1.24, 95% CI 1.05-1.48) This association was consistent when BMI was modeled as a continuous variable (Figure). Rates of stroke or systemic embolism did not differ significantly across BMI categories (0.9-1.1% per year). There was no interaction of BMI with the reduction in stroke or systemic embolism with apixaban vs. aspirin (p int=0.37). Major bleeding occurred at rates of 1.9% (normal BMI), 1.2% (overweight) and 1.2% (obesity) per year. Compared to patients with normal BMI (aHR 0.90, 95% CI 0.55-1.50), the increase in major bleeding with apixaban vs. aspirin was more pronounced in patients who had overweight (aHR 1.97, 95% CI 1.18-3.29) and obesity (aHR 1.29, 95% CI 0.75-2.20) (p int=0.09). Conclusions In patients with SCAF <24 hours, a higher BMI was associated with arrhythmia progression. The reduction in stroke with apixaban vs. aspirin was consistent across BMI categories. The additional increase in bleeding with apixaban appeared to be more pronounced in patients who had overweight and obesity.