Dataset for amiodarone adverse events compared to placebo using data from randomized controlled trials

The dataset presented here provides a detailed description of the adverse events of amiodarone versus placebo using data from 43 randomized controlled trials. Two authors (M.M., M.R.) independently extracted the data. The dataset also includes baseline patient characteristics, amiodarone loading and maintenance doses, as well as forest plots describing the relative risk (RR) of developing an adverse event related to the pulmonary, thyroid, hepatic, cardiac, skin, gastrointestinal, neurological, and ocular systems. The Mantel-Haenszel random effects model was used to determine the relative risk of adverse events of amiodarone compared to placebo. This dataset is complementary to our article “Meta-analysis Comparing the Relative Risk of Adverse Events for Amiodarone Versus Placebo”, which was published in the American Journal of Cardiology [1]. The data can be used to assess certain adverse events and their relation to amiodarone loading and/or maintenance dose.


Data
The raw dataset contains the number of events and number of patient-year for the amiodarone and placebo arm of each study (reads in xlsx format, each organ system in a separate sheet). Patients' characteristics are summarized in Tables 1 and 2. The number and incident rate of events are listed in Table 4. The rate of adverse events in the amiodarone arm for each organ system, and the rate of drug discontinuation compared to placebo are illustrated in Figs. 1e9.

Experimental design, materials, and methods
The protocol was developed by three authors (M.M., M.R., A.F.) and revised by all authors. PubMed, Google Scholar, the Cochrane Central Register for randomized controlled trials, and ClinicalTrials.gov were searched for studies that analyzed the use of amiodarone regardless of indication or efficacy of therapy (latest search was conducted on October 10, 2018). Articles were identified using key search terms: amiodarone, adverse events, side effects, placebo, atrial fibrillation, atrial flutter, ventricular tachycardia, arrhythmias, liver, skin, thyroid, eye, and lung. Specifications Table   Subject Cardiology and Cardiovascular Medicine Specific subject area A meta-analysis reporting the relative risk of developing adverse events related to amiodarone compared to placebo Type of data Value of the Data This dataset provides detailed description of the adverse events and its relative risk in patients taking amiodarone compared to placebo. This is very important for the medical community as amiodarone is one of commonly used drugs to treat atrial fibrillation. Medical providers who are prescribing or managing patients taking amiodarone as well as researchers interested in assessing amiodarone related adverse events. Further analysis could be performed to determine how different amiodarone loading and maintenance regimens could affect the development of amiodarone related adverse events. Understanding the nature and the rate of amiodarone related adverse events will help physicians develop appropriate screening and monitoring strategies for these events.   Table 2 Baseline patient characteristics. Forty-three randomized control trials [2e20] were studied, and 11,395 patients were included (5792 patients in the amiodarone group, 5603 patients in the placebo group). Average age was 62.0 years for patients receiving amiodarone and 62.3 years for patients receiving placebo. Follow up time ranged from 12e54 months in studies with follow up 12 months. Indications for amiodarone therapy were suppression of atrial and ventricular arrhythmias, and maintenance dose for amiodarone ranged from 200 to 600 mg daily. Raw data for the adverse events is provided in the supplement material.  Low risk Meyer 1993 Low risk Mahmarian 1994 Low risk Donovan 1995 Low risk Singh 1995 Low risk Galve 1996 Low risk Gentile 1996 Low risk Cairns 1997 Low risk Daoud 1997 Low risk Julian 1997 Low risk Singh 1997 Low risk Kochiadakis 1998 Low risk Cotter 1999 Low risk Kochiadakis 1999 Low risk Redle 1999 Low risk Bianconi 2000 Low risk Elizari 2000 Low risk Kochiadakis 2000 Low risk Lee 2000 Low risk References of all identified studies were also hand-searched for inclusion to identify additional relevant studies [1]. All articles were then independently reviewed for inclusion in this analysis by two authors (M.M., M.R.). Inclusion criteria were: 1) randomized control trial, 2) documentation of adverse events and drug discontinuation due to adverse events, 3) presence of placebo arm. Data on sample size, follow up, and outcomes were then extracted. Discrepancies were discussed and resolved by consensus.
Primary outcomes of this analysis were pulmonary, hepatic, thyroid, ocular, cardiac, skin, and neurological adverse events, as well as drug discontinuation related to adverse side effects. Specific adverse events within each organ system were also reported. All adverse events were presented as incident rate per 10,000 person-years.
The Cochrane Risk of Bias table and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) System were utilized to determine risk of bias and quality of the outcomes in all trials incorporated into this analysis (Table 3).
RevMan version 5.3 (The Nordic Cochrane Center, The Cochrane Collaboration; Copenhagen, Denmark) was used to conduct the primary analysis. Relative risk (RR) was determined for all studies using the Mantel-Haenszel random effects model with 95% confidence interval (CI) to establish the likelihood of adverse events. A secondary analysis was also performed to determine the RR for studies with follow up < 12 months and 12 months. Sensitivity analyses were used to show the robustness of the results. Heterogeneity was calculated using I 2 , a value which represents the percentage of variability in the effect risk estimate among studies due to heterogeneity rather than chance (I 2 <25% considered as low, I 2 between 25% and 75% as intermediate, I 2 >75% considered as high). Begg's funnel plots method was utilized to investigate potential publication bias. A p-value of <0.05 was used to determine statistical significance.         8. Ocular adverse events. "Total" represents total events per 10,000 person-years. The incident rate of ocular adverse events per 10,000 person-years was higher in patients receiving amiodarone versus placebo; however, this never reached statistical significance (37 vs 10; RR: 3.01; 95% CI [0.87e10.36], P ¼ 0.08, I 2 : 30%).