title: Anti-arrhythmic medications increase non-cardiac mortality - A meta-analysis of randomized control trials.
abstract: BACKGROUND
  Anti-arrhythmic medications (AAMs) are known to increase cardiac mortality significantly due to their pro-arrhythmic effects. However, the effect of AAMs on non-cardiac mortality has not been evaluated.
  
  
  METHODS
  Trials published in English language journals from 1990 to 2015 were thoroughly retrieved by searching websites such as PubMed, Medline, Cochrane Library, and Google Scholar. Randomized controlled trials reporting non-cardiac deaths as primary or secondary outcomes were used to compare AAMs to non-arrhythmic therapy (AV nodal blocking agents, implantable cardiovascular defibrillation (ICD), or placebo). Information regarding the sample size, treatment type, baseline characteristics, and outcomes was obtained by using a standardized protocol. The fixed effect model was used to perform meta-analysis, and results were expressed in terms of odds ratio (OR) with confidence interval (CI) of 95%, inter study heterogeneity was assessed using I (2). Intention to treat principle was applied to extract data.
  
  
  RESULTS
  Total of 18,728 patients were enrolled in 15 trials; 9359 patients received AAMs and 9369 received non-arrhythmic therapy. AAMs were associated with an increased risk of non-cardiac mortality (OR=1.30, [95% CI: 1.12, 1.50], p=0.0005, I (2) index=24%) and all-cause mortality (OR=1.09, [95% CI: 1.01, 1.18], p=0.04, I (2)=54%) as compared to non-arrhythmic therapy. There was no difference in the cardiac mortality (OR=1.01, [95% CI: 0.92, 1.11], p=0.82, I (2)=53%) or arrhythmic mortality (OR=1.00, [95% CI: 0.89, 1.13], p=0.94, I (2)=64%) between the two groups.
  
  
  CONCLUSIONS
  AAMs are associated with an increased risk of non-cardiac and all-cause mortality. The effect of AAMs, especially amiodarone, on non-cardiac mortality requires further evaluation.
authors.affiliation: Department of Internal Medicine, Staten Island University Hospital, USA.
authors.forename: Bhavi
authors.initials: B
authors.lastname: Pandya
authors.affiliation: Department of Internal Medicine, Staten Island University Hospital, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Spagnola
authors.affiliation: Department of Internal Medicine, Staten Island University Hospital, USA.
authors.forename: Azfar
authors.initials: A
authors.lastname: Sheikh
authors.affiliation: Department of Internal Medicine, Staten Island University Hospital, USA.
authors.forename: Boutros
authors.initials: B
authors.lastname: Karam
authors.affiliation: Department of Internal Medicine, Staten Island University Hospital, USA.
authors.forename: Viswajit Reddy
authors.initials: VR
authors.lastname: Anugu
authors.affiliation: Department of Internal Medicine, Staten Island University Hospital, USA.
authors.forename: Asif
authors.initials: A
authors.lastname: Khan
authors.affiliation: Department of Cardiology, Staten Island University Hospital, USA.
authors.forename: James
authors.initials: J
authors.lastname: Lafferty
authors.affiliation: Florida Heart Rhythm Specialist, Plantation, FL, USA.
authors.forename: David
authors.initials: D
authors.lastname: Kenigsberg
authors.affiliation: Department of Cardiology, Staten Island University Hospital, USA.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kowalski
keywords: Anti-arrhythmic medications; ICD; Meta-analysis; Non-cardiac mortality