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Trends in Cardiovascular Medicine Jul 2019Although amiodarone is considered the most effective antiarrhythmic agent, its use is limited by a wide variety of potential toxicities. The purpose of this review is to...
Although amiodarone is considered the most effective antiarrhythmic agent, its use is limited by a wide variety of potential toxicities. The purpose of this review is to provide a comprehensive "bench to bedside" overview of the ways amiodarone influences thyroid function. We performed a systematic search of MEDLINE to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and other clinically relevant studies. The search was limited to English-language reports published between 1950 and 2017. Amiodarone was searched using the terms adverse effects, hypothyroidism, myxedema, hyperthyroidism, thyroid storm, atrial fibrillation, ventricular arrhythmia, and electrical storm. Google and Google scholar as well as bibliographies of identified articles were reviewed for additional references. We included 163 germane references in this review. Because amiodarone is one of the most frequently prescribed antiarrhythmic drugs in the United States, the mechanistic, diagnostic and therapeutic information provided is relevant for practicing clinicians in a wide range of medical specialties.
Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Humans; Predictive Value of Tests; Prognosis; Risk Assessment; Thyroid Diseases; Thyroid Function Tests; Thyroid Gland
PubMed: 30309693
DOI: 10.1016/j.tcm.2018.09.005 -
Journal of Clinical Medicine Oct 2018Drug-induced interstitial lung disease (DIILD) occurs as a result of numerous agents, but the risk often only becomes apparent after the marketing authorisation of such... (Review)
Review
BACKGROUND
Drug-induced interstitial lung disease (DIILD) occurs as a result of numerous agents, but the risk often only becomes apparent after the marketing authorisation of such agents.
METHODS
In this PRISMA-compliant systematic review, we aimed to evaluate and synthesise the current literature on DIILD.
RESULTS
Following a quality assessment, 156 full-text papers describing more than 6000 DIILD cases were included in the review. However, the majority of the papers were of low or very low quality in relation to the review question (78%). Thus, it was not possible to perform a meta-analysis, and descriptive review was undertaken instead. DIILD incidence rates varied between 4.1 and 12.4 cases/million/year. DIILD accounted for 3⁻5% of prevalent ILD cases. Cancer drugs, followed by rheumatology drugs, amiodarone and antibiotics, were the most common causes of DIILD. The radiopathological phenotype of DIILD varied between and within agents, and no typical radiological pattern specific to DIILD was identified. Mortality rates of over 50% were reported in some studies. Severity at presentation was the most reliable predictor of mortality. Glucocorticoids (GCs) were commonly used to treat DIILD, but no prospective studies examined their effect on outcome.
CONCLUSIONS
Overall high-quality evidence in DIILD is lacking, and the current review will inform larger prospective studies to investigate the diagnosis and management of DIILD.
PubMed: 30326612
DOI: 10.3390/jcm7100356 -
The Cochrane Database of Systematic... Sep 2019Atrial fibrillation is the most frequent sustained arrhythmia. Atrial fibrillation often recurs after restoration of normal sinus rhythm. Antiarrhythmic drugs have been...
BACKGROUND
Atrial fibrillation is the most frequent sustained arrhythmia. Atrial fibrillation often recurs after restoration of normal sinus rhythm. Antiarrhythmic drugs have been widely used to prevent recurrence. This is an update of a review previously published in 2006, 2012 and 2015.
OBJECTIVES
To determine the effects of long-term treatment with antiarrhythmic drugs on death, stroke, drug adverse effects and recurrence of atrial fibrillation in people who had recovered sinus rhythm after having atrial fibrillation.
SEARCH METHODS
We updated the searches of CENTRAL, MEDLINE and Embase in January 2019, and ClinicalTrials.gov and WHO ICTRP in February 2019. We checked the reference lists of retrieved articles, recent reviews and meta-analyses.
SELECTION CRITERIA
Two authors independently selected randomised controlled trials (RCTs) comparing any antiarrhythmic drug with a control (no treatment, placebo, drugs for rate control) or with another antiarrhythmic drug in adults who had atrial fibrillation and in whom sinus rhythm was restored, spontaneously or by any intervention. We excluded postoperative atrial fibrillation.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed quality and extracted data. We pooled studies, if appropriate, using Mantel-Haenszel risk ratios (RR), with 95% confidence intervals (CI). All results were calculated at one year of follow-up or the nearest time point.
MAIN RESULTS
This update included one new study (100 participants) and excluded one previously included study because of double publication. Finally, we included 59 RCTs comprising 20,981 participants studying quinidine, disopyramide, propafenone, flecainide, metoprolol, amiodarone, dofetilide, dronedarone and sotalol. Overall, mean follow-up was 10.2 months.All-cause mortalityHigh-certainty evidence from five RCTs indicated that treatment with sotalol was associated with a higher all-cause mortality rate compared with placebo or no treatment (RR 2.23, 95% CI 1.03 to 4.81; participants = 1882). The number need to treat for an additional harmful outcome (NNTH) for sotalol was 102 participants treated for one year to have one additional death. Low-certainty evidence from six RCTs suggested that risk of mortality may be higher in people taking quinidine (RR 2.01, 95% CI 0.84 to 4.77; participants = 1646). Moderate-certainty evidence showed increased RR for mortality but with very wide CIs for metoprolol (RR 2.02, 95% CI 0.37 to 11.05, 2 RCTs, participants = 562) and amiodarone (RR 1.66, 95% CI 0.55 to 4.99, 2 RCTs, participants = 444), compared with placebo.We found little or no difference in mortality with dofetilide (RR 0.98, 95% CI 0.76 to 1.27; moderate-certainty evidence) or dronedarone (RR 0.86, 95% CI 0.68 to 1.09; high-certainty evidence) compared to placebo/no treatment. There were few data on mortality for disopyramide, flecainide and propafenone, making impossible a reliable estimation for those drugs.Withdrawals due to adverse eventsAll analysed drugs increased withdrawals due to adverse effects compared to placebo or no treatment (quinidine: RR 1.56, 95% CI 0.87 to 2.78; disopyramide: RR 3.68, 95% CI 0.95 to 14.24; propafenone: RR 1.62, 95% CI 1.07 to 2.46; flecainide: RR 15.41, 95% CI 0.91 to 260.19; metoprolol: RR 3.47, 95% CI 1.48 to 8.15; amiodarone: RR 6.70, 95% CI 1.91 to 23.45; dofetilide: RR 1.77, 95% CI 0.75 to 4.18; dronedarone: RR 1.58, 95% CI 1.34 to 1.85; sotalol: RR 1.95, 95% CI 1.23 to 3.11). Certainty of the evidence for this outcome was low for disopyramide, amiodarone, dofetilide and flecainide; moderate to high for the remaining drugs.ProarrhythmiaVirtually all studied antiarrhythmics showed increased proarrhythmic effects (counting both tachyarrhythmias and bradyarrhythmias attributable to treatment) (quinidine: RR 2.05, 95% CI 0.95 to 4.41; disopyramide: no data; flecainide: RR 4.80, 95% CI 1.30 to 17.77; metoprolol: RR 18.14, 95% CI 2.42 to 135.66; amiodarone: RR 2.22, 95% CI 0.71 to 6.96; dofetilide: RR 5.50, 95% CI 1.33 to 22.76; dronedarone: RR 1.95, 95% CI 0.77 to 4.98; sotalol: RR 3.55, 95% CI 2.16 to 5.83); with the exception of propafenone (RR 1.32, 95% CI 0.39 to 4.47) for which the certainty of evidence was very low and we were uncertain about the effect. Certainty of the evidence for this outcome for the other drugs was moderate to high.StrokeEleven studies reported stroke outcomes with quinidine, disopyramide, flecainide, amiodarone, dronedarone and sotalol. High-certainty evidence from two RCTs suggested that dronedarone may be associated with reduced risk of stroke (RR 0.66, 95% CI 0.47 to 0.95; participants = 5872). This result is attributed to one study dominating the meta-analysis and has yet to be reproduced in other studies. There was no apparent effect on stroke rates with the other antiarrhythmics.Recurrence of atrial fibrillationModerate- to high-certainty evidence, with the exception of disopyramide which was low-certainty evidence, showed that all analysed drugs, including metoprolol, reduced recurrence of atrial fibrillation (quinidine: RR 0.83, 95% CI 0.78 to 0.88; disopyramide: RR 0.77, 95% CI 0.59 to 1.01; propafenone: RR 0.67, 95% CI 0.61 to 0.74; flecainide: RR 0.65, 95% CI 0.55 to 0.77; metoprolol: RR 0.83 95% CI 0.68 to 1.02; amiodarone: RR 0.52, 95% CI 0.46 to 0.58; dofetilide: RR 0.72, 95% CI 0.61 to 0.85; dronedarone: RR 0.85, 95% CI 0.80 to 0.91; sotalol: RR 0.83, 95% CI 0.80 to 0.87). Despite this reduction, atrial fibrillation still recurred in 43% to 67% of people treated with antiarrhythmics.
AUTHORS' CONCLUSIONS
There is high-certainty evidence of increased mortality associated with sotalol treatment, and low-certainty evidence suggesting increased mortality with quinidine, when used for maintaining sinus rhythm in people with atrial fibrillation. We found few data on mortality in people taking disopyramide, flecainide and propafenone, so it was not possible to make a reliable estimation of the mortality risk for these drugs. However, we did find moderate-certainty evidence of marked increases in proarrhythmia and adverse effects with flecainide.Overall, there is evidence showing that antiarrhythmic drugs increase adverse events, increase proarrhythmic events and some antiarrhythmics may increase mortality. Conversely, although they reduce recurrences of atrial fibrillation, there is no evidence of any benefit on other clinical outcomes, compared with placebo or no treatment.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Electric Countershock; Humans; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention
PubMed: 31483500
DOI: 10.1002/14651858.CD005049.pub5 -
BMJ Clinical Evidence Aug 2011Heart failure occurs in 3% to 4% of adults aged over 65 years, usually as a consequence of coronary artery disease or hypertension, and causes breathlessness, effort... (Review)
Review
INTRODUCTION
Heart failure occurs in 3% to 4% of adults aged over 65 years, usually as a consequence of coronary artery disease or hypertension, and causes breathlessness, effort intolerance, fluid retention, and increased mortality. The 5-year mortality in people with systolic heart failure ranges from 25% to 75%, often owing to sudden death following ventricular arrhythmia. Risks of cardiovascular events are increased in people with left ventricular systolic dysfunction (LVSD) or heart failure.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of multidisciplinary interventions for heart failure? What are the effects of exercise in people with heart failure? What are the effects of drug treatments for heart failure? What are the effects of devices for treatment of heart failure? What are the effects of coronary revascularisation for treatment of heart failure? What are the effects of drug treatments in people at high risk of heart failure? What are the effects of treatments for diastolic heart failure? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 80 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: aldosterone receptor antagonists, amiodarone, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, anticoagulation, antiplatelet agents, beta-blockers, calcium channel blockers, cardiac resynchronisation therapy, coronary revascularisation, digoxin (in people already receiving diuretics and angiotensin-converting enzyme inhibitors), exercise, hydralazine plus isosorbide dinitrate, implantable cardiac defibrillators, multidisciplinary interventions, non-amiodarone antiarrhythmic drugs, and positive inotropes (other than digoxin).
Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiac Resynchronization Therapy; Heart Failure; Humans; Ventricular Dysfunction, Left
PubMed: 21878135
DOI: No ID Found -
BMJ Clinical Evidence Feb 2010Heart failure occurs in 3% to 4% of adults aged over 65 years, usually as a consequence of coronary artery disease or hypertension, and causes breathlessness, effort... (Review)
Review
INTRODUCTION
Heart failure occurs in 3% to 4% of adults aged over 65 years, usually as a consequence of coronary artery disease or hypertension, and causes breathlessness, effort intolerance, fluid retention, and increased mortality. The 5-year mortality in people with systolic heart failure ranges from 25% to 75%, often owing to sudden death following ventricular arrhythmia. Risks of cardiovascular events are increased in people with left ventricular systolic dysfunction (LVSD) or heart failure.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug treatments, and of drug and invasive treatments, for heart failure? What are the effects of angiotensin-converting enzyme inhibitors in people at high risk of heart failure? What are the effects of treatments for diastolic heart failure? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 85 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: aldosterone receptor antagonists; amiodarone; angiotensin-converting enzyme inhibitors; angiotensin II receptor blockers; anticoagulation; antiplatelet agents; beta-blockers; calcium channel blockers; cardiac resynchronisation therapy; digoxin (in people already receiving diuretics and angiotensin-converting enzyme inhibitors); exercise; hydralazine plus isosorbide dinitrate; implantable cardiac defibrillators; multidisciplinary interventions; non-amiodarone antiarrhythmic drugs; and positive inotropes (other than digoxin).
Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Treatment Outcome; Ventricular Dysfunction, Left
PubMed: 21718583
DOI: No ID Found -
CJC Open Jan 2021Observational studies have identified inconsistent associations between chronic use of amiodarone and cancer-related outcomes. We performed a systematic review and... (Review)
Review
BACKGROUND
Observational studies have identified inconsistent associations between chronic use of amiodarone and cancer-related outcomes. We performed a systematic review and meta-analysis to evaluate cancer risk among patients receiving amiodarone.
METHODS
We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) to May 1, 2020. We included randomized controlled trials (RCTs) with follow-up ≥2 years that compared amiodarone (any dose) to any comparator (placebo, active pharmacologic or interventional comparator, or usual care), and reported ≥1 outcome of interest. We contacted authors of published chronic amiodarone trials for potentially unreported cancer outcomes. The primary outcome was cancer incidence. Secondary outcomes were cancer-related death and site-specific cancers. We determined risk ratios and 95% confidence intervals using a fixed-effect model, and statistical heterogeneity using . We conducted prespecified subgroup and sensitivity analyses for amiodarone indication, amiodarone dose, duration of therapy, and trial-level risk of bias.
RESULTS
From 1439 articles, we included 5 RCTs (n = 4357). Mean follow-up duration ranged from 21 to 37 months. We included previously unpublished cancer outcome data from 1 RCT. Our primary outcome was not reported in any RCT. There was no significant difference in cancer-related death between amiodarone (1.69%) and the comparator (1.75%) (risk ratio 0.96, 95% confidence interval 0.57-1.63; = 0%). There were no significant interactions from our subgroup or sensitivity analyses.
CONCLUSIONS
Chronic amiodarone use did not increase cancer-related deaths. Data from RCTs do not support an increased risk of cancer-related harms with amiodarone use, and these concerns should not deter use of amiodarone when indicated.
PubMed: 33458637
DOI: 10.1016/j.cjco.2020.09.013 -
Cureus Nov 2023A review of the literature was made to find and choose research papers, on drugs (amiodarone and adenosine) used for managing supraventricular tachycardia (SVT) in... (Review)
Review
A review of the literature was made to find and choose research papers, on drugs (amiodarone and adenosine) used for managing supraventricular tachycardia (SVT) in children and infants (one hour to 17 years of age) with no structural heart disease by PRISMA guideline. Our team conducted an exhaustive systematic literature review (SLR), utilizing an extensive search methodology across recognized databases like PubMed, PubMed Central, Google Scholar, Web of Science, and The Cochrane Library. We included 10 scholarly articles that satisfied our rigorous selection criteria including systematic reviews/meta-analysis, and randomized control trials, shedding light on treatment with amiodarone and adenosine for SVT in pediatric patients. There is no first- or second-line treatment for SVT in pediatrics, and drug effectiveness can vary significantly between patients. Adenosine has a shorter half-life than other drugs, instead, it is safer and more valuable when an electrocardiogram is uncertain, it is recommended as an acute management, and it continues as the first-line option for paroxysmal SVT. Amiodarone management patients with acute STV within, its use showed better results when administered 48 hours after diagnosis. Furthermore, it is recommended to reduce the incidence of junctional ectopic tachycardia (JET), by pre-operative prophylaxis, also for chronic control in this and other types of SVT. In none of the evaluated studies were documented significant adverse effects in pediatric patients. Side effects that did occur were mild and easily managed. The studies also emphasize that although both amiodarone and adenosine can successfully convert SVT to sinus rhythm, better results have been observed when using combined therapies of each recommended medication. Therefore, more randomized clinical trials, meta-analyses, and systematic reviews are needed to solidify and possibly standardize an effective and safe pharmacological treatment for SVT and its types in pediatric patients.
PubMed: 38073952
DOI: 10.7759/cureus.48507 -
BMJ Clinical Evidence Feb 2011Acute atrial fibrillation is rapid, irregular, and chaotic atrial activity of less than 48 hours' duration. Risk factors for acute atrial fibrillation include increasing... (Review)
Review
INTRODUCTION
Acute atrial fibrillation is rapid, irregular, and chaotic atrial activity of less than 48 hours' duration. Risk factors for acute atrial fibrillation include increasing age, cardiovascular disease, alcohol, diabetes, and lung disease. Acute atrial fibrillation increases the risk of stroke and heart failure. The condition resolves spontaneously within 24 to 48 hours in over 50% of people; however, many people will require interventions to control heart rate or restore sinus rhythm.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent embolism, for conversion to sinus rhythm, and to control heart rate in people with recent-onset atrial fibrillation (within 7 days) who are haemodynamically stable? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 30 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: amiodarone, antithrombotic treatment before cardioversion, digoxin, diltiazem, direct current cardioversion, flecainide, propafenone, quinidine, sotalol, timolol, and verapamil.
Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Humans; Propafenone; Sotalol
PubMed: 21718559
DOI: No ID Found -
BMJ Clinical Evidence Nov 2014Acute atrial fibrillation is rapid, irregular, and chaotic atrial activity of recent onset. Various definitions of acute atrial fibrillation have been used in the... (Review)
Review
INTRODUCTION
Acute atrial fibrillation is rapid, irregular, and chaotic atrial activity of recent onset. Various definitions of acute atrial fibrillation have been used in the literature, but for the purposes of this review we have included studies where atrial fibrillation may have occurred up to 7 days previously. Risk factors for acute atrial fibrillation include increasing age, cardiovascular disease, alcohol, diabetes, and lung disease. Acute atrial fibrillation increases the risk of stroke and heart failure. The condition resolves spontaneously within 24 to 48 hours in more than 50% of people; however, many people will require interventions to control heart rate or restore sinus rhythm.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent embolism, for conversion to sinus rhythm, and to control heart rate in people with recent-onset atrial fibrillation (within 7 days) who are haemodynamically stable? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 26 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: amiodarone, antithrombotic treatment before cardioversion, atenolol, bisoprolol, carvedilol, digoxin, diltiazem, direct current cardioversion, flecainide, metoprolol, nebivolol, propafenone, sotalol, timolol, and verapamil.
Topics: Acute Disease; Anti-Arrhythmia Agents; Atrial Fibrillation; Electric Countershock; Humans; Safety
PubMed: 25430048
DOI: No ID Found -
The Journal of Innovations in Cardiac... Apr 2020Amiodarone is commonly used for a variety of arrhythmias and, in some parts of the world, is the only available antiarrhythmic drug (AAD). Yet, amiodarone is known to...
Amiodarone is commonly used for a variety of arrhythmias and, in some parts of the world, is the only available antiarrhythmic drug (AAD). Yet, amiodarone is known to have a wide range of potential side effects, many of which are dose- and duration-dependent. We sought to study the incidence of side effects leading to the discontinuation of low-dose amiodarone, arbitrarily defined as 200 mg/day or less, and very-low-dose amiodarone, defined as 100 mg/day or less. In this study, literature databases were searched through June 2019. Studies that reported the incidence or prevalence of side effects of amiodarone were included. Effect estimates from individual studies were extracted and combined using the random-effects generic inverse variance method of DerSimonian and Laird. A total of 10 observational cohort studies involving 901 patients were included in the analysis. The pooled estimated incidence of overall side effects for low-dose amiodarone was 0.17 [95% confidence interval (CI): 0.12-0.22]. In addition, the pooled estimated incidence of side effects requiring medication discontinuation was 0.06 (95% CI: 0.03-0.11). As compared with 200 mg/day of amiodarone, the pooled estimated incidence of overall side effects was 0.11 (95% CI: 0.04-0.27), while the incidence of side effects requiring medication discontinuation was 0.02 (95% CI: 0.01-0.06) for the dose of 100 mg/day. In conclusion, very-low-dose amiodarone displays a low incidence of significant side effects requiring medication discontinuation.
PubMed: 32368381
DOI: 10.19102/icrm.2020.110403