Abstract
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.
Keywords: Amiodarone, Adverse events, Toxicity
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 | Tables Figures Raw data (supplement) |
| How data were acquired | We searched PubMed, Google Scholar, the Cochrane Central Register for RCTs, and ClinicalTrials.gov for studies that evaluated amiodarone use irrespective of indication or efficacy of amiodarone therapy |
| Data format | Raw, Analyzed, Filtered |
| Parameters for data collection | Patients who took amiodarone for prevention and/or treatment of ventricular or atrial arrhythmias. |
| Description of data collection | We searched PubMed, Google Scholar, the Cochrane Central Register for RCTs, and ClinicalTrials.gov for studies that evaluated amiodarone use irrespective of indication or efficacy of amiodarone therapy. Key search terms used were amiodarone, adverse events, side effects, placebo, atrial fibrillation, atrial flutter, ventricular tachycardia, arrhythmias, liver, hepatic, skin, thyroid, eye, and lung, and pulmonary. Bibliographies of retrieved studies were hand-searched to identify additional relevant studies. |
| Data source location | Data from randomized controlled trials. |
| Data accessibility | With the article, and the supplement. |
| Related research article | Ruzieh M, Moroi MK, Aboujamous NM, Ghahramani M, Naccarelli GV, Mandrola J, Foy AJ. Meta-Analysis Comparing the Relative Risk of Adverse Events for Amiodarone Versus Placebo. Am J Cardiol. 2019. pii: S0002-9149(19)31046-X. https://doi.org/10.1016/j.amjcard.2019.09.008. [Epub ahead of print] |
Value of the Data
|
1. 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 Table 1, Table 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 Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5, Fig. 6, Fig. 7, Fig. 8, Fig. 9.
Table 1.
Baseline patient characteristics. Forty-three randomized control trials [[2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20]] 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 1 week–6 months for 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.
| Amiodarone arm |
Placebo arm |
|||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First author | Year | Medical condition | Average Ejection fraction | Percent with IHD | Reason for intervention | Mean follow-up (days) |
Average Load Dose (mg/day) |
Load (# of days) |
Average Maintenance Dose (mg/day) | Maintenance (# of days) |
No. Of Pts |
Mean age (yrs) | Male Gender (%) | No. Of Pts |
Mean age (yrs) | Male Gender (%) |
| Greco | 1989 | Patients with anterior MI | NA | 100% | Reduce mortality and morbidity | Until discharge | 10–20 mg/kg | 1 | N/A | N/A | 159 | 54 | 85 | 160 | 55 | 87 |
| Hamer | 1989 | Congestive heart failure | 18% | 60% | Arrhythmia control, exercise tolerance and ventricular function | 180 | 387 | 180 | 200 | 150 | 16 | 70 | N/A | 14 | 66 | N/A |
| Hohnloser | 1991 | Post CABG | NA | 100% | Suppression of SVT and ventricular arrhythmias | 4 | 1125 | 4 | N/A | N/A | 39 | 59 | 76.9 | 38 | 59 | 73.7 |
| Meyer | 1993 | Stable angina | 59% | 100% | Limiting angina pectoris | 60 | 400 | 30 | 200 | 50 | 32 | 61 | N/A | 31 | 58 | N/A |
| Mahmarian | 1994 | Systolic heart failure and NSVT | 24% | 49% | Suppression of ventricular arrhythmias | 90 | 422 | 30 | 50 or 100 | 54 | 32 | 53.5 | 77.5 | 16 | 51 | 81 |
| Donovan | 1995 | Patients with recent-onset AF | NA | 48% | Restoration of sinus rhythm | Until discharge | 7 mg/kg | 1 | N/A | N/A | 32 | 56 | N/A | 32 | 59 | N/A |
| Galve | 1996 | Newly diagnosed AF | NA | NA | Rhythm control | 15 | 1200 + 5 mg/kg | 1 | N/A | N/A | 50 | 60 | 54 | 50 | 61 | 56 |
| Gentile | 1996 | Elderly patients with systolic heart failure | <40% | 61% | Reduce sudden cardiac death | 180 | 400 | 30 | 100 | 150 | 24 | 71 | N/A | 22 | 71 | N/A |
| Daoud | 1997 | Patients undergoing open heart surgery | 48% | 60% | Prevention of post-op AF | 30 | 200–1000 | 13 ± 7 | N/A | N/A | 64 | 57 | 68.8 | 60 | 67 | 66.7 |
| Kochiadakis | 1998 | Patients with recent onset AF | 50% | NA | Restoration of sinus rhythm | 1 | 2100 + 20 mg/kg | 1 | N/A | N/A | 48 | 63 | 56 | 49 | 65 | 51 |
| Cotter | 1999 | Patients with paroxysmal AF | Majority <45% | 43% | Restoration of sinus rhythm | 30 | 3000 | 1 | N/A | N/A | 50 | 64.5 | 48 | 50 | 68 | 38 |
| Kochiadakis | 1999 | Patients with persistent AF | 50% | NA | Restoration of sinus rhythm | 30 | 460 + 20 mg/kg | 28 | N/A | N/A | 33 | 64 | 48.5 | 34 | 63 | 47.1 |
| Redle | 1999 | Patients undergoing CABG | 49% | 100% | Prevention of post-op AF | 10 | 430 | 11 | N/A | N/A | 73 | 63 | 83.5 | 70 | 64.5 | 81.4 |
| Bianconi | 2000 | Patients with AF or AFL | NA | 15% | Acute termination of AF or flutter | 3–7 | 5 mg/kg | 1 | N/A | N/A | 54 | 63 | 57 | 54 | 66 | 54 |
| Elizari | 2000 | Patients with acute MI | NA | 100% | Reduce morbidity/mortality | 180 | 900 | 3 | N/A | N/A | 542 | 60.3 | 80.6 | 531 | 60.5 | 75.1 |
| Lee | 2000 | Patients undergoing CABG | 59% | 100% | Prevention of post-op AF | 18 | 150 + 0.4/kg | 8 | N/A | N/A | 74 | 66 | 54 | 76 | 65 | 55 |
| Peuhkurinen | 2000 | Patients with recent-onset AF | 63% | 21% | Restoration of sinus rhythm | 1 | 30 mg/kg | 1 | N/A | N/A | 31 | 56 | 81 | 31 | 62 | 65 |
| Vardas | 2000 | Patients with AF | 51% | NA | Restoration of sinus rhythm | 30 | 600 | 28 | N/A | N/A | 108 | 64 | 49.1 | 100 | 65 | 49 |
| Giri | 2001 | Patients undergoing CABG, valve or combined | 43% | 98% | Prevention of post-op AF | 9 | 1000 | 6; 10 | N/A | N/A | 120 | 72.7 | 78 | 100 | 72.5 | 74 |
| Maras | 2001 | Patients undergoing CABG | 44% | 100% | Prevention of post-op AF | 7 | 325 | 8 | N/A | N/A | 159 | 58.3 | 80 | 156 | 57.3 | 76 |
| White | 2002 | Patients undergoing open heart surgery | 43% | 35% | Prevention of post-op AF | 21–42 | 1200–1400 | >10; >6 | N/A | N/A | 120 | 72.6 | 78.3 | 100 | 72.5 | 74 |
| Yagdi | 2003 | Patients undergoing CABG | 48% | 100% | Prevention of post-op AF | 30 | 400-600 + 10/kg | 2; 5; 5 | N/A | N/A | 77 | 59.3 | 80.5 | 80 | 61.1 | 73.7 |
| Auer | 2004 | Patients undergoing open heart surgery | 69% | 64% | Prevention of post-op AF | 12 | 667 | 9 | N/A | N/A | 63 | 64 | 58.7 | 65 | 63 | 58.5 |
| Mitchell | 2005 | Patients undergoing CABG, valve replacement, repair | 58% | 75% | Prevention of post-op atrial tachyarrhythmia | 13 | 10 mg/kg | 13 | N/A | N/A | 299 | 61.3 | 82.6 | 302 | 61.9 | 81.8 |
| Alcalde | 2006 | Patients undergoing CABG | 53% | 100% | Prevention of post-op AF & AFL | 10 | 1800 | 1–3 | N/A | N/A | 46 | 61 | 63 | 47 | 61.1 | 70.2 |
| Budeus | 2006 | Patients undergoing CABG | 63% | 100% | Prevention of post-op AF | 0.5 | 640 | 7 | N/A | N/A | 55 | 64.9 | 87.3 | 55 | 66.7 | 76.4 |
| Zebis | 2007 | Patients undergoing CABG | 55% | 100% | Prevention of post-op AF | 30 | 1200 | 5 | N/A | N/A | 125 | 67 | 86 | 125 | 67 | 80 |
| Gu | 2009 | Patients undergoing off-pump CABG | 61% | 100% | Prevention of post-op AF | 21 | 200 + 70 mg/kg | 17 | N/A | N/A | 100 | 73.6 | 75 | 110 | 74.2 | 72 |
| Balla | 2011 | Newly diagnosed AF | NA | NA | Rhythm control for AF | 1 | 30 mg/kg | 1 | N/A | N/A | 40 | 58.9 | 72.5 | 40 | 58.6 | 60 |
| Khitri | 2012 | AF, AFL | 59% | 15% | Rhythm control | 90 | 330 | 30 | 200 | 60 | 108 | 64.9 | 73.1 | 162 | 62.4 | 64.9 |
| Riber | 2013 | Lung cancer surgery | NA | 2% | Prevention of post-op AF | 30 | 1200 | 5 | N/A | N/A | 122 | 66 | 49 | 120 | 67 | 47 |
| Darkner | 2014 | AF patients undergoing RFA | 50% | 7% | Rhythm control after ablation | 180 | 400 | 30 | 200 | 26 | 104 | 62 | 81 | 108 | 61 | 86 |
AF: Atrial fibrillation, AFL: Atrial flutter, CABG: Coronary artery bypass graft, IHD: Ischemic heart disease, MI: myocardial infarction, NA: Not available, NSVT: Non-sustained ventricular tachycardia, RFA: Radiofrequency ablation.
Table 2.
Baseline patient characteristics. Forty-three randomized control trials [[2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20]] 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 12–54 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.
| Amiodarone arm |
Placebo arm |
|||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First author | Year | Medical condition | Average ejection fraction | Percent with IHD | Reason for intervention | Mean follow-up (months) | Average Load dose (mg/day) | Average Load (day) | Average maintenance dose (mg) | Average maintenance (days) | No. of Pts | Mean age (year) | Male Gender (%) | No. of Pts | Mean age (year) | Male Gender (%) |
| Nicklas | 1991 | Heart failure and frequent ventricular ectopy | 20% | 52% | Reduce sudden cardiac death | 12 | 400 | 28 | 200 | 215 | 49 | 56 | 83.7 | 52 | 59 | 86.5 |
| Ceremuzynski | 1992 | Post MI | Majority > 40% | 100% | Reduce mortality and ventricular arrhythmias | 12 | 800 | 7 | 200–400 | 306 | 305 | 59.4 | 71.1 | 308 | 58.6 | 68.2 |
| Singh[36] | 1995 | Patients with CHF and vent arrhythmia | <40% | 71% | Improve mortality | 45 | 800 | 14 | 328 | 1246 | 336 | 65 | 99.1 | 338 | 66.1 | 98.8 |
| Cairns | 1997 | Survivors of MI with frequent or repetitive PVCs | NA | 100% | Resuscitated ventricular fibrillation or arrhythmic death | 21.5 | 20/kg | 14 | 200–400 | 365–730 | 606 | 64 | 82.5 | 596 | 64 | 82 |
| Julian | 1997 | Survivors of MI and EF ≤ 40% | 30% | 35% | All-cause mortality | 21 | 450 | 112 | 200 | 253–618 | 743 | 59.6 | 83.8 | 743 | 60.2 | 84.9 |
| Singh | 1997 | Patients with CHF, COPD and patients undergoing surgery | 25–30% | NA | Evaluate pulmonary toxicity | 45 | 800 | 14 | 300–400 | 365–1620 | 269 | 65 | N/A | 250 | 65.8 | N/A |
| Kochiadakis | 2000 | Paroxysmal AF | 55% | NA | Rhythm control | 22 | 12.5/kg | 14 | 200 | 720 | 65 | 63.2 | 52.3 | 60 | 62.8 | 51.7 |
| Channer | 2004 | Persistent AF undergoing DCCV | 59% | 30% | Rhythm control | 54 | 800 | 14 | 200 | 364 | 61 | 66 | 77 | 38 | 68 | 79 |
| Vora | 2004 | Patients with chronic rheumatic AF | 56% | NA | Rhythm or rate control | 12 | 600 | 10 | 200 | 355 | 48 | 39.5 | 47.9 | 48 | 38 | 45.8 |
| Singh | 2005 | Persistent AF | 50% | 25% | Rhythm control | 12–54 | 700 | 28 | 200–300 | >365 | 267 | 67.1 | 99.3 | 137 | 67.7 | 99.3 |
| Vilvanathan | 2016 | AF in patients post BMV | 58% | 1% | Rhythm control for AF | 12 | 500 | 28 | 200 | 365 | 44 | 38.8 | 20.5 | 45 | 37.62 | 34.1 |
AF: Atrial fibrillation, BMV: balloon mitral valvuloplasty, CHF: congestive heart failure, COPD: chronic obstructive pulmonary disease, DCCV: direct current cardioversion, EF: Ejection fraction, IHD: Ischemic heart disease, MI: myocardial infarction, NA: Not available, PVC: premature ventricular contraction.
Table 4.
Number of events, incident rate, and relative risk of specific adverse events for amiodarone compared to placebo.
| organ system | Follow up ≥ 12 months, No. of events (events/10,000 patient year) |
All, No. of events (events/10,000 patient year) |
||||||
|---|---|---|---|---|---|---|---|---|
| Amiodarone arm | Placebo | RR (95% CI), P value | Amiodarone arm | Placebo | RR (95% CI), P value | |||
| Pulmonary adverse events | Pulmonary fibrosis | 8 (13) | 6 (11) | 8 (12) | 6 (11) | |||
| Cough | 0 (0) | 0 (0) | 1 (1) | 0 (0) | ||||
| Lung infiltrates | 0 (0) | 0 (0) | 1 (1) | 0 (0) | ||||
| Unspecified | 77 (124) | 40 (70) | 77 (115) | 40 (65) | ||||
| Total | 85 (136) | 46 (81) | 1.74 (1.21–2.50), 0.003 | 87 (129) | 46 (74) | 1.77 (1.24–2.52), 0.002 | ||
| Thyroid adverse events | Clinical hyperthyroidism | 19 (36) | 4 (8) | 19 (33) | 5 (9) | |||
| Clinical hypothyroidism | 27 (52) | 0 (0) | 27 (47) | 0 (0) | ||||
| Subclinical change in TFT | 13 (25) | 3 (6) | 40 (70) | 8 (15) | ||||
| Unspecified | 24 (46) | 5 (11) | 29 (51) | 9 (17) | ||||
| Total | 83 (159) | 12 (25) | 5.32 (2.99–9.44), < 0.001 | 115 (201) | 22 (42) | 4.44 (2.87–6.89), < 0.001 | ||
| Liver adverse events | Liver failure | 0 (0) | 0 (0) | 0 (0) | 0 (0) | |||
| Elevated liver enzymes | 8 (15) | 3 (6) | 10 (18) | 5 (10) | ||||
| Unspecified | 21 (40) | 8 (17) | 21 (37) | 8 (15) | ||||
| Total | 29 (56) | 11 (23) | 2.42 (1.23–4.74), 0.01 | 31 (54) | 13 (25) | 2.27 (1.20–4.29), 0.01 | ||
| Cardiac adverse events | Bradyarrhythmias | 100 (192) | 34 (72) | 267 (468) | 128 (244) | |||
| Hypotension | 0 (0) | 0 (0) | 98 (172) | 65 (124) | ||||
| Long QT | 5 (10) | 0 (0) | 18 (32) | 0 (0) | ||||
| Torsade de pointes | 0 (0) | 0 (0) | 0 (0) | 0 (0) | ||||
| Worsening heart failure | 1 (2) | 1 (2) | 5 (9) | 5 (10) | ||||
| Unspecified conduction disease | 0 (0) | 0 (0) | 46 (81) | 32 (61) | ||||
| Unspecified | 0 (0) | 0 (0) | 6 (11) | 6 (11) | ||||
| Total | 106 (203) | 35 (74) | 2.76 (1.91–3.98), < 0.001 | 440 (771) | 236 (450) | 1.94 (1.39–2.71) < 0.001 | ||
| Skin adverse events | Blue/gray discoloration of skin | 2 (4) | 3 (6) | 2 (4) | 3 (6) | |||
| Photosensitivity | 1 (2) | 0 (0) | 11 (19) | 0 (0) | ||||
| Unspecified rash/flushing | 21 (40) | 9 (19) | 33 (58) | 9 (17) | ||||
| Total | 24 (46) | 12 (25) | 1.51 (0.73–3.11), 0.26 | 46 (81) | 12 (23) | 1.99 (1.04–3.78), 0.04 | ||
| GI adverse events | Dyspepsia/nausea/vomiting | 20 (38) | 16 (34) | 122 (214) | 74 (141) | |||
| Diarrhea | 0 (0) | 0 (0) | 8 (14) | 4 (8) | ||||
| Unspecified | 35 (67) | 25 (53) | 62 (109) | 33 (63) | ||||
| Total | 55 (105) | 41 (86) | 1.36 (0.91–2.04), 0.14 | 192 (336) | 111 (212) | 1.63 (1.18–2.24), 0.003 | ||
| Neuro adverse events | Ataxia or gait disturbances | 17 (33) | 6 (13) | 17 (30) | 6 (11) | |||
| Headache | 0 (0) | 0 (0) | 25 (44) | 17 (32) | ||||
| Dizziness | 0 (0) | 0 (0) | 7 (12) | 4 (8) | ||||
| Tremor | 2 (4) | 0 (0) | 2 (4) | 0 (0) | ||||
| Peripheral neuropathy | 0 (0) | 0 (0) | 1 (2) | 0 (0) | ||||
| Unspecified | 29 (56) | 13 (27) | 29 (51) | 13 (25) | ||||
| Total | 48 (92) | 19 (40) | 2.35 (1.38–4.00), 0.002 | 81 (140) | 40 (76) | 1.93 (1.41–2.65), < 0.001 | ||
| Ocular adverse events | Corneal microdeposits | 9 (17) | 0 (0) | 9 (16) | 0 (0) | |||
| Blurred vision | 0 (0) | 0 (0) | 1 (2) | 0 (0) | ||||
| Blue vision spots | 0 (0) | 0 (0) | 1 (2) | 0 (0) | ||||
| Unspecified | 10 (19) | 5 (11) | 10 (18) | 5 (10) | ||||
| Total | 19 (36) | 5 (11) | 4.41 (0.48–40.86), 0.19 | 21 (37) | 5 (10) | 3.01 (0.87–10.36), 0.08 | ||
| Drug discontinuation | 552 (1230) | 284 (650) | 2.01 (1.46–2.78), < 0.001 | 795 (1614) | 431(896) | 1.79 (1.45–2.19), < 0.001 | ||
Fig. 1.
Pulmonary adverse events. “Total” represents total events per 10,000 person-years. The incident rate of pulmonary adverse events per 10,000 person-years was higher in the amiodarone group versus placebo (129 vs 74; RR: 1.77; 95% CI [1.24–2.52], P = 0.002, 12: 0%).
Fig. 2.
Thyroid adverse events. “Total” represents total events per 10,000 person-years. The incident rate of thyroid adverse events per 10,000 person-years was higher in the amiodarone group versus placebo (201 vs 42; RR: 4.44; 95% CI [2.87–6.89], P < 0.001, 12: 0%).
Fig. 3.
Liver adverse events. “Total represents total events per 10,000 person-years. Liver adverse events were rare, but the rate of liver adverse events per 10,000 person-years was still higher in the amiodarone group versus placebo (54 vs 25; RR: 2.27; 95% CI [1.20–4.29], P = 0.01, I2: 0%).
Fig. 4.
Cardiac adverse events. “Total” represents total events per 10,000 person-years. Cardiac adverse events were the most commonly reported adverse events for both groups. The incident rate of cardiac adverse events per 10,000 person-years was higher in patients receiving amiodarone versus placebo (771 vs 450; RR: 1.94; 95% CI [1.39–2.71], P = 0.0001, I2: 23%).
Fig. 5.
Skin adverse events. “Total” represents total events per 10,000 person-years. The incident rate of skin adverse events was higher in the amiodarone group versus placebo (81 vs 23; RR: 1.99; 95% CI [1.04–3.78], P = 0.04, I2: 0%).
Fig. 6.
Gastrointestinal adverse events. “Total” represents total events per 10,000 person-years. The incident rate of gastrointestinal adverse events was higher in patients receiving amiodarone compared to those receiving placebo (336 vs 212; RR: 1.63; 95% CI [1.18–2.24], P = 0.003, I2: 14%).
Fig. 7.
Neurological adverse events. “Total” represents total events per 10,000 person-years. The incident rate of neurological adverse events per 10,000 person-years was higher in the amiodarone group versus placebo (140 vs 76; RR: 1.93; 95% CI [1.41–2.65], P < 0.001, 12: 0%).
Fig. 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 [0.87–10.36], P = 0.08, I2: 30%).
Fig. 9.
Rates of drug discontinuation. “Total” represents total events per 10,000 person-years. The incident rate of drug discontinuation secondary to side effects per 10,000 person-years was higher in the amiodarone group versus placebo (1614 vs 896; RR: 1.79; 95% CI [1.45–2.19], P < 0.001, I2: 43%).
2. 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. 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).
Table 3.
Risk of bias. Majority of trials included in this analysis were double blinded, decreasing both performance and detection biases.
Highlighted are studies with follow up ≥ 12 months.
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 I2, a value which represents the percentage of variability in the effect risk estimate among studies due to heterogeneity rather than chance (I2 <25% considered as low, I2 between 25% and 75% as intermediate, I2 >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.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.dib.2019.104835.
Conflict of Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Appendix A. Supplementary data
The following is the Supplementary data to this article:
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