Dabigatran Use and Cerebrovascular Event Risk Across Body Mass Index in Atrial Fibrillation: A Real-World Nested Case-Control Study

Abstract

Dabigatran is widely used for stroke prevention in atrial fibrillation (AF), but concerns remain regarding its effectiveness in patients with Class III obesity ( BMI ≥40 kg/m2.) We evaluated the association between dabigatran use in patients with AF and ischaemic stroke (IS) or transient ischaemic attack (TIA) across body mass index (BMI) categories in a multiethnic New Zealand population. In this retrospective nested case-control study, cases with incident IS/TIA were identified from the fifth Auckland Regional Community Stroke Study (1st September 2020-31st August 2021), and event-free controls were randomly selected from the National Minimum Dataset. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) for IS/TIA, and effect modification by BMI catergory (< 30, 30-39.9, ≥40 kg/m2) was assessed using an interaction term. Among 1,854 patients with AF (295 cases, 1,559 controls), dabigatran use was associated with lower odds of IS/TIA (adjusted odds ratio [aOR] 0.50, 95% CI 0.38-0.68). After multivariable adjustment, BMI was not independently associated with IS/TIA risk. The association between dabigatran use and lower IS/TIA risk was similar in patients with BMI <30 and 30-39.9 kg/m2, but the point estimate shifted towards the null in patients with BMI ≥40 kg/m2 and was imprecise. There was no statistical evidence of effect modification by BMI (p-interaction=0.49), although clinically important attenuation in Class III obesity could not be excluded. In this real-world nested case-control study, there was no clear statistical evidence of BMI-related effect modification; however, the study had limited power in patients with BMI ≥40 kg/m2, and clinically important attenuation, including the possibility of no reduction in IS/TIA odds with dabigatran use in Class III obesity cannot be excluded.