Association Between Amiodarone Use and Survival in NVAF Patients

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Association Between Use of Amiodarone for Non-Valvular Atrial Fibrillation and Patient Survival: Insights from the Prospective China Atrial Fibrillation Registry

Introduction

Atrial fibrillation (AF) is a significant global health burden, impairing quality of life and increasing risks of morbidity and mortality. Management strategies for AF have historically focused on rhythm control using antiarrhythmic drugs (AADs) or rate control combined with antithrombotic therapy. Amiodarone, a widely prescribed AAD, has been a cornerstone for maintaining sinus rhythm. However, conflicting evidence exists regarding its association with patient survival. A post-hoc analysis of the AFFIRM trial suggested that amiodarone might increase mortality risks, raising concerns about its safety. This study evaluated the real-world association between amiodarone use and all-cause mortality in non-valvular atrial fibrillation (NVAF) patients using data from the China Atrial Fibrillation (China-AF) Registry, reflecting contemporary clinical practices.

Study Design and Population

The China-AF Registry is a prospective, multicenter, hospital-based study enrolling 20,666 patients from 31 hospitals in Beijing between 2011 and 2017. For this analysis, 8,161 NVAF patients who were AAD-naive before enrollment were included. Exclusion criteria included valvular AF, prior AAD use, catheter/surgical ablation during index hospitalization, or insufficient follow-up. Patients were categorized into two groups: the amiodarone group (689 patients receiving amiodarone at enrollment or during follow-up) and the non-AAD group (6,167 patients without class I/III AAD use). Follow-up occurred at 3, 6, and subsequent 6-month intervals, with outcomes tracked through clinic visits or telephone interviews.

Baseline Characteristics

The amiodarone group was younger (mean age 65.6 vs. 68.6 years) and had fewer comorbidities, including lower rates of chronic heart failure (CHF, 18.6% vs. 26.0%), prior bleeding (3.3% vs. 5.5%), and stroke/TIA/thromboembolism (15.1% vs. 21.2%). Patients receiving amiodarone were more likely to have higher education levels, be treated in tertiary hospitals (80.6% vs. 77.0%), and present with paroxysmal AF (55.6% vs. 38.8%). Conversely, persistent AF was less common in the amiodarone group (27.3% vs. 50.1%). Oral anticoagulant (OAC) use was lower in the amiodarone group (16.3% vs. 22.3%), reflecting potential underutilization in rhythm-control strategies.

Primary Outcome: All-Cause Mortality

Over a mean follow-up of 300.6 ± 77.5 days, the amiodarone group showed a numerically lower incidence of all-cause mortality (2.44 vs. 3.91 per 100 person-years), but this difference was not statistically significant (adjusted hazard ratio [aHR] 0.79, 95% CI 0.42–1.49). Multivariable Cox regression adjusted for age, comorbidities, OAC use, and hospital level identified independent mortality predictors:

  • Increased risk: Age (aHR 1.04 per year), CHF (aHR 1.85), prior stroke/TIA (aHR 1.33), abnormal liver function (aHR 2.59), eGFR <60 mL/min/1.73 m² (aHR 2.07), and hospitalization (aHR 4.30).
  • Reduced risk: Body mass index (aHR 0.92 per kg/m²), hyperlipidemia (aHR 0.70), tertiary hospital care (aHR 0.56), and OAC use (aHR 0.49).

Subgroup analyses stratified by age, sex, prior CAD, CHF, AF type, and time since diagnosis confirmed no significant survival benefit with amiodarone.

Secondary Outcome: Sinus Rhythm Maintenance

Amiodarone demonstrated superior efficacy in maintaining sinus rhythm. At the penultimate follow-up, 55.7% of the amiodarone group remained in sinus rhythm compared to 40.1% in the non-AAD group (P <0.001). This benefit was consistent across subgroups, including younger patients (59.5% vs. 44.8% in those <65 years) and those without CHF (57.4% vs. 41.7%).

Discussion

Key Findings in Context

This study found no significant association between amiodarone use and reduced 1-year mortality in NVAF patients, despite its effectiveness in maintaining sinus rhythm. These results contrast with the AFFIRM trial’s post-hoc analysis, which linked amiodarone to higher mortality. Potential explanations include differences in patient demographics and clinical practices:

  1. Younger, Healthier Cohort: The amiodarone group had lower rates of CHF, CAD, and persistent AF compared to AFFIRM participants, possibly attenuating mortality risks.
  2. Lower Digoxin Use: Digoxin, associated with increased mortality, was less frequently prescribed in this cohort (8.9% vs. 32.9% in AFFIRM).
  3. Real-World Practice: The study reflects contemporary management, including lower OAC use in rhythm-control strategies, which may influence outcomes.

Clinical Implications

The findings suggest that amiodarone’s benefits in rhythm control do not translate into survival advantages in unselected NVAF populations. This aligns with prior trials showing no mortality difference between rhythm and rate control. However, the higher sinus rhythm maintenance rate with amiodarone highlights its role in improving symptomatic outcomes, particularly in younger patients or those with paroxysmal AF.

Limitations

  1. Observational Design: Residual confounding from unmeasured variables (e.g., AF symptom severity) may persist.
  2. Short Follow-Up: The mean follow-up of 10 months limits assessment of long-term outcomes.
  3. Dosing Data: Cumulative amiodarone doses and toxicity risks were not analyzed.
  4. Regional Focus: Results may not generalize to non-Chinese populations due to differences in OAC utilization and healthcare practices.

Conclusion

In the China-AF Registry, amiodarone use was not associated with reduced 1-year mortality in NVAF patients, despite effective sinus rhythm maintenance. These findings underscore the need for personalized treatment decisions, balancing symptom control against potential risks. Future studies should explore long-term outcomes and the role of newer AADs or ablation therapies in improving survival.

doi.org/10.1097/CM9.0000000000001270

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