Rate and rhythm therapy in patients with atrial fibrillation and the risk of pacing and bradyarrhythmia

Heart Rhythm. 2019 Sep;16(9):1348-1356. doi: 10.1016/j.hrthm.2019.05.018. Epub 2019 May 21.

Abstract

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.

Keywords: Antiarrhythmic drugs; Atrial fibrillation; Bradyarrhythmia; Pacemaker; Rate-lowering drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Amiodarone* / administration & dosage
  • Amiodarone* / adverse effects
  • Anti-Arrhythmia Agents* / administration & dosage
  • Anti-Arrhythmia Agents* / adverse effects
  • Anti-Arrhythmia Agents* / classification
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / epidemiology
  • Atrial Fibrillation / physiopathology
  • Bradycardia* / chemically induced
  • Bradycardia* / diagnosis
  • Bradycardia* / epidemiology
  • Denmark / epidemiology
  • Female
  • Heart Rate / drug effects*
  • Hospitalization / statistics & numerical data
  • Humans
  • Long Term Adverse Effects* / chemically induced
  • Long Term Adverse Effects* / diagnosis
  • Long Term Adverse Effects* / epidemiology
  • Male
  • Patient Care Management / methods
  • Patient Care Management / statistics & numerical data
  • Registries
  • Risk Assessment
  • Risk Factors
  • Sex Factors

Substances

  • Anti-Arrhythmia Agents
  • Amiodarone