Risk of Amiodarone-Induced Pulmonary Toxicity Versus Placebo in Patients with Cardiac Arrhythmias and Heart Failure: A Meta-Analysis of Randomised Controlled Trials
DOI:
https://doi.org/10.37275/bsm.v10i8.1641Keywords:
Amiodarone, Interstitial lung disease, Meta-analysis, Pulmonary toxicity, Randomised controlled trialsAbstract
Background: Amiodarone is the most effective antiarrhythmic agent for maintaining sinus rhythm, yet its long-term use is constrained by extracardiac toxicity, of which pulmonary toxicity is the most feared because it carries appreciable mortality and is frequently misdiagnosed. No contemporary meta-analysis has isolated amiodarone-induced pulmonary toxicity as the single primary endpoint across cardiac arrhythmia and heart-failure populations; this study quantified that risk.
Methods: PubMed/MEDLINE, Scopus and Web of Science were searched for placebo- or usual-care-controlled randomised controlled trials (RCTs) of oral amiodarone in adults with cardiac arrhythmia or heart-failure indications reporting pulmonary toxicity. Two reviewers extracted 2×2 data and assessed risk of bias with Cochrane RoB 2.0. Because the outcome was dichotomous, the risk ratio (RR) was pooled using a DerSimonian–Laird random-effects model, with the odds ratio (OR) and Peto OR as corroborative measures.
Results: Nine RCTs comprising 6,209 patients (3,175 amiodarone; 3,034 control) were included. Pulmonary toxicity occurred in 77 of 3,175 amiodarone-treated patients (2.43%) versus 42 of 3,034 controls (1.38%). Amiodarone significantly increased pulmonary-toxicity risk (RR 1.70, 95% CI 1.17–2.45, p = 0.005), with no detectable heterogeneity (I² = 0%). The OR (1.74) and Peto OR (1.81) were concordant, and the estimate remained harmful under every single-study deletion (RR 1.46–2.64). Higher-dose strata showed a numerically larger effect (RR 2.50) than lower-dose strata (RR 1.69; subgroup p = 0.48).
Conclusion: Amiodarone was associated with an approximately 70% relative increase in pulmonary-toxicity risk versus placebo, a robust and homogeneous finding. The absolute excess was modest (about one additional case per 95 patients treated), supporting continued use with structured baseline and periodic pulmonary surveillance, particularly at higher maintenance doses and longer durations.
Authors
- Dzaki Murtadho1*
- Dewi Wahyu Fitrina1
- Deddy Herman1
- 1Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Andalas, Padang, Indonesia
Corresponding author Dzaki Murtadho — Dzakiimrd@outlook.com
Article history
- Submitted
- Accepted
- Published
Downloads
Published
Issue
Section
License
As our aim is to disseminate original research article, hence the publishing right is a necessary one. The publishing right is needed in order to reach the agreement between the author and publisher. As the journal is fully open access, the authors will sign an exclusive license agreement.
The authors have the right to:
- Share their article in the same ways permitted to third parties under the relevant user license.
- Retain copyright, patent, trademark and other intellectual property rights including research data.
- Proper attribution and credit for the published work.
For the open access article, the publisher is granted to the following right.
- The non-exclusive right to publish the article and grant right to others.
- For the published article, the publisher applied for the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
