Rate- and Rhythm Therapy in Patients with Atrial Fibrillation and the Risk of Pacing and Bradyarrhythmia

Background: Management of atrial fibrillation (AF) with rate and rhythm therapy can cause bradyarrhythmia. Objectives: To assess overall risk, temporal risk, and subgroup at risk of bradyarrhythmia-related events by rate and/or rhythm therapy drugs. Methods: Using Danish nationwide registries, patients with AF between 2000 and 2014 were included if prescribed with rate-lowering drugs (RLDs) or antiarrhythmic drugs (AADs). An adjusted time-dependent Poisson regression model estimated the association between RLDs and AADs with a composite endpoint of pacemaker, temporary pacing, and bradyarrhythmia hospitalization. Secondary outcomes were each individual event. Results: Among 135,017 AF patients, 9196 (6.8%) patients experienced the composite endpoint with a median follow-up of 3.7 (interquartile range [IQR]: 1.6–7.0) years. Median age was 74 (IQR: 65–82) years and 47.6% were women. With rate-lowering monotherapy as the reference, the incidence rate ratios (IRR) (95% confidence interval) for the composite endpoint were 1.36 (1.29–1.43) for rate-lowering dual therapy, 1.62 (1.43–1.84) for antiarrhythmic monotherapy, and 2.49 (2.29–2.71) for AAD combined with RLDs. Similar trend was found for each secondary outcome. Particularly amiodarone increased the risk. This association was strongest within the first 2 weeks of treatment. In those treated with AAD combined with RLDs, high-risk populations were patients ≥70 years (IRR: 3.35 [2.51–4.45] compared to patients <60 years), and women (IRR: 1.35 [1.15–1.57], compared to men). Conclusions: In real-world AF patients, rate-lowering dual therapy, antiarrhythmic monotherapy, and AADs combined with RLDs were positively associated with bradyarrhythmia-related events. The risk was highest in those treated with amiodarone, in the initial 2 weeks of treatment, in women, and in the elderly.