-
Therapeutic Advances in Ophthalmology 2023Amiodarone is widely used for heart arrhytmia. Previous studies have suggested the possibility of optic neuropathy with the chronic use of this drug.
BACKGROUND
Amiodarone is widely used for heart arrhytmia. Previous studies have suggested the possibility of optic neuropathy with the chronic use of this drug.
OBJECTIVES
To identify structural or functional changes in the retina and optic nerve in patients on chronic amiodarone therapy without visual complaints.
METHODS
This observational study included 15 eyes of 15 patients with cardiac arrythmia on chronic amiodarone treatment and 15 healthy matched subjects as a control group. All subjects underwent electrophysiological tests [pattern visual evoked potential (PVEP), pattern electroretinogram (PERG), multifocal electroretinogram (mfERG), and optical coherence tomography (OCT) and angiography (OCTA)].
RESULTS
There were no statistically significant differences between the two groups regarding the PVEP, PERG, and the mfERG parameters. Macular and optic nerve head OCT and OCTA have not shown statistically significant differences except for the morphological parameters of the optic disc ( = 0.008 for the horizontal and = 0.013 for vertical cup/disc ratio and = 0.045 for rim area).
CONCLUSION
Patients on chronic amiodarone therapy have not shown evident structural or functional changes in the retinal or optic nerve as demonstrated by electrophysiological tests, OCT, and OCTA results compared to controls.
PubMed: 37701727
DOI: 10.1177/25158414231194159 -
Clinical Pharmacology : Advances and... 2023Dronedarone is an effective drug for maintaining the sinus rhythm in patients with atrial fibrillation (AF). The efficacy and safety of dronedarone versus amiodarone in...
BACKGROUND
Dronedarone is an effective drug for maintaining the sinus rhythm in patients with atrial fibrillation (AF). The efficacy and safety of dronedarone versus amiodarone in patients with AF after catheter ablation (CA) needs more evidence. We retrospectively compared the efficacy and safety of dronedarone and amiodarone in our hospital.
METHODS
Patients who underwent CA from January 2021 to January 2022 and used dronedarone (n=229) or amiodarone (n=202) during the blind period were enrolled. The recurrence of AF in post-and during the blanking period was compared between the groups; the rehospitalization for re-ablation and adverse drug events (ADE) were also calculated.
RESULTS
During an average follow-up period of 14.28 months, the long-term recurrence rate of AF did not differ significantly between the amiodarone group and dronedarone group (22.71% vs 21.29%, hazard ratio [HR], 1.033, 95% confidence interval [CI], 0.661-1.614; p=0.888). The recurrence rate in the blanking period also showed no statistically significant differences between the amiodarone group and dronedarone group (9.90% vs 14.41%, HR, 0.851; 95% CI, 0.463-1.564; p=0.604). The re-hospitalization rates for re-ablation between two groups did not differ between the amiodarone group and dronedarone group (4.65% vs 13.46%; p =0.144). The incidence of ADE was higher in the dronedarone groups than that in the amiodarone group (16.59% vs 5.45%, p <0.001). The main adverse drug events in the dronedarone and amiodarone groups were gastrointestinal (6.99%) and bradycardia (2.48%), respectively.
CONCLUSION
Compared to the amiodarone group, the dronedarone group had a similar blank-period and long-term recurrence rate of AF and a higher incidence of ADE.
PubMed: 38090388
DOI: 10.2147/CPAA.S440704 -
Iranian Journal of Basic Medical... 2024Lipid-based drug delivery systems (DDS) can improve the pharmacokinetic (PK) parameters of some drugs. Especially those with a high volume of distribution (Vd) leading...
How do lipid-based drug delivery systems affect the pharmacokinetic and tissue distribution of amiodarone? A comparative study of liposomes, solid lipid nanoparticles, and nanoemulsions.
OBJECTIVES
Lipid-based drug delivery systems (DDS) can improve the pharmacokinetic (PK) parameters of some drugs. Especially those with a high volume of distribution (Vd) leading to off-target accumulation and toxicity. Amiodarone as an anti-arrhythmic agent induces hypothyroidism and liver disorders limiting its clinical indication.
MATERIALS AND METHODS
In the present study, amiodarone PK parameters and biodistribution after IV administration of four nano-formulations to rats were compared. The formulations were liposomes, solid lipid nanoparticles (SLN), PEGylated SLN (PEG-SLN), and nanoemulsions (NE). All formulations were optimized.
RESULTS
The nanoparticles were spherical with a diameter of 100-200 nm and sustained drug release in buffer pH 7.4. The best-fitted model for the plasma concentration-time profile was two-compartmental. studies indicated the most changes in PKs induced after liposome, SLN, and NE administration, respectively. The area under the curve (AUC) and maximum plasma concentration (C) of liposomes, SLN, and NE were 22.5, 2.6, 2.46 times, and 916, 58, and 26 times higher than that of amiodarone solution, respectively (<0.05). The heart-to-liver ratio of amiodarone was higher for nano-formulations compared to drug solution except for liposomes.
CONCLUSION
Lipid-based particles can improve the PK parameters of amiodarone and its distribution in different tissues.
PubMed: 38800017
DOI: 10.22038/IJBMS.2024.75152.16292 -
Toxicology and Applied Pharmacology Oct 2023Cardiac and extra-cardiac side effects of common antiarrhythmic agents might be related to drug-induced mitochondrial dysfunction. Supratherapeutic doses of amiodarone...
Cardiac and extra-cardiac side effects of common antiarrhythmic agents might be related to drug-induced mitochondrial dysfunction. Supratherapeutic doses of amiodarone have been shown to impair mitochondria in animal studies, whilst influence of propafenone on cellular bioenergetics is unknown. We aimed to assess effects of protracted exposure to pharmacologically relevant doses of amiodarone and propafenone on cellular bioenergetics and mitochondrial biology of human and mouse cardiomyocytes. In this study, HL-1 mouse atrial cardiomyocytes and primary human cardiomyocytes derived from the ventricles of the adult heart were exposed to 2 and 7 μg/mL of either amiodarone or propafenone. After 24 h, extracellular flux analysis and confocal laser scanning microscopy were used to measure mitochondrial functions. Autophagy was assessed by western blots and live-cell imaging of lysosomes. In human cardiomyocytes, amiodarone significantly reduced mitochondrial membrane potential and ATP production, in association with an inhibition of fatty acid oxidation and impaired complex I- and II-linked respiration in the electron transport chain. Expectedly, this led to increased anaerobic glycolysis. Amiodarone increased the production of reactive oxygen species and autophagy was also markedly affected. In contrast, propafenone-exposed cardiomyocytes did not exert any impairment of cellular bioenergetics. Similar changes after amiodarone treatment were observed during identical experiments performed on HL-1 mouse cardiomyocytes, suggesting a comparable pharmacodynamics of amiodarone among mammalian species. In conclusion, amiodarone but not propafenone in near-therapeutic concentrations causes a pattern of mitochondrial dysfunction with affected autophagy and metabolic switch from oxidative metabolism to anaerobic glycolysis in human cardiomyocytes.
PubMed: 37661063
DOI: 10.1016/j.taap.2023.116676 -
Journal of Clinical Pharmacology Dec 2023Amiodarone is an antiarrhythmic drug with a significant adverse effect profile, including neurotoxicity. While ataxia, neuropathy, and tremors are more commonly seen... (Review)
Review
Amiodarone is an antiarrhythmic drug with a significant adverse effect profile, including neurotoxicity. While ataxia, neuropathy, and tremors are more commonly seen forms of amiodarone neurotoxicity, very few cases of nystagmus are reported. We report the case of an 86-year-old man who presented with abrupt-onset ataxia, dizziness, and inability to ambulate, 10 days after initiating amiodarone for atrial fibrillation. His examination revealed gaze-evoked nystagmus along with features of cerebellar dysfunction. After excluding other etiologies, amiodarone was stopped. His nystagmus resolved, and his ataxia improved within 48 h of stopping amiodarone. Due to the rarity of this drug-induced adverse effect, we performed a systematic review of available case reports in the literature (PubMed and Scopus) using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and presented our findings. Nystagmus is a rarely reported adverse effect of amiodarone, which can occur within days to months of starting the medication. Treatment includes stopping the drug and monitoring for resolution of nystagmus.
Topics: Aged, 80 and over; Humans; Male; Amiodarone; Anti-Arrhythmia Agents; Ataxia; Atrial Fibrillation; Dizziness; Drug-Related Side Effects and Adverse Reactions; Tremor; Case Reports as Topic
PubMed: 37571970
DOI: 10.1002/jcph.2330 -
The Annals of Pharmacotherapy Nov 2023Rivaroxaban and amiodarone are commonly used for treating patients with atrial fibrillation. Drug-drug interactions between rivaroxaban and amiodarone may increase...
BACKGROUND
Rivaroxaban and amiodarone are commonly used for treating patients with atrial fibrillation. Drug-drug interactions between rivaroxaban and amiodarone may increase exposure to rivaroxaban. However, the clinical relevance of this drug-drug interaction is still not clear.
OBJECTIVE
The aim was to investigate the risk of bleeding in patients receiving a combination of rivaroxaban and amiodarone.
METHODS
This was a prospective observational study in which we included atrial fibrillation patients treated with rivaroxaban. The patients were divided into the rivaroxaban group and the combination of rivaroxaban and amiodarone group (the combination group). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust between-group differences. The primary endpoint was defined as the time to the first occurrence of a composite of major, clinically relevant nonmajor, and minor bleeding.
RESULTS
In total, 481 atrial fibrillation patients were included in the analysis. After PSM, 154 patients in the rivaroxaban group were matched with 154 patients in the combination group. The bleeding events mainly consisted of clinically relevant nonmajor and minor bleeding. Only one patient experienced major bleeding. The primary outcome was recorded in 26.0% of patients in the combination group and 10.4% of patients in the rivaroxaban group (hazard ratio = 2.76, 95% CI = 1.55-4.93, < 0.001). The bleeding risk was significantly higher in the combination group compared with that in the rivaroxaban group in the IPTW and stabilized IPTW analyses (hazard ratio = 2.17, 95% CI = 1.32-3.56, = 0.002).
CONCLUSION AND RELEVANCE
The combination of rivaroxaban and amiodarone increased the risk of bleeding in patients with atrial fibrillation, especially clinically relevant nonmajor and minor bleeding. Physicians prescribing rivaroxaban and amiodarone together should be concerned about an increase in the risk of nonmajor bleeding.
PubMed: 37960871
DOI: 10.1177/10600280231211306 -
American Journal of Cardiovascular... Jul 2023Since atrial fibrillation (AF) is one of the major arrhythmias managed in hospitals worldwide, it has a major impact on public health. The guidelines agree on the... (Meta-Analysis)
Meta-Analysis
PURPOSE
Since atrial fibrillation (AF) is one of the major arrhythmias managed in hospitals worldwide, it has a major impact on public health. The guidelines agree on the desirability of cardioverting paroxysmal AF episodes. This meta-analysis aims to answer the question of which antiarrhythmic agent is most effective in cardioverting a paroxysmal AF.
MATERIALS AND METHODS
A systematic review and Bayesian network meta-analysis, searching MEDLINE, Embase, and CINAHL, were performed, including randomized controlled trials (RCTs) enrolling a population of unselected adult patients with a paroxysmal AF that compared at least two pharmacological regimes to restore the sinus rhythm or a cardioversion agent against a placebo. The main outcome was efficacy in restoring sinus rhythm.
RESULTS
Sixty-one RCTs (7988 patients) were included in the quantitative analysis [deviance information criterion (DIC) 272.57; I = 3%]. Compared with the placebo, the association verapamil-quinidine shows the highest SUCRA rank score (87%), followed by antazoline (86%), vernakalant (85%), tedisamil at high dose (i.e., 0.6 mg/kg; 80%), amiodarone-ranolazine (80%), lidocaine (78%), dofetilide (77%), and intravenous flecainide (71%). Taking into account the degree of evidence of each individual comparison between pharmacological agents, we have drawn up a ranking of pharmacological agents from the most effective to the least effective.
CONCLUSIONS
In comparing the antiarrhythmic agents used to restore sinus rhythm in the case of paroxysmal AF, vernakalant, amiodarone-ranolazine, flecainide, and ibutilide are the most effective medications. The verapamil-quinidine combination seems promising, though few RCTs have studied it. The incidence of side effects must be taken into account in the choice of antiarrhythmic in clinical practice.
CLINICAL TRIAL REGISTRATION
PROSPERO: International prospective register of systematic reviews, 2022, CRD42022369433 (Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022369433 ).
Topics: Adult; Humans; Atrial Fibrillation; Quinidine; Flecainide; Electric Countershock; Ranolazine; Network Meta-Analysis; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Anti-Arrhythmia Agents; Amiodarone; Verapamil
PubMed: 37233967
DOI: 10.1007/s40256-023-00586-5 -
Journal of Cardiovascular Development... Aug 2023Cardiac amyloidosis (CA) is a rare but potentially life-threatening disease in which misfolded proteins accumulate in the cardiac wall tissue. Heart rhythm disorders in... (Review)
Review
Cardiac amyloidosis (CA) is a rare but potentially life-threatening disease in which misfolded proteins accumulate in the cardiac wall tissue. Heart rhythm disorders in CA, including supraventricular arrhythmias, conduction system disturbances, or ventricular arrhythmias, play a major role in CA morbidity and mortality, and thus require supplementary management. Among them, AF is the most frequent arrhythmia during CA hospitalizations and is associated with significantly higher mortality, while ventricular arrhythmias are also common and are usually associated with poor prognosis. Early diagnosis of potential arrythmias could be performed through ECG, Holter monitoring, and/or electrophysiology study. Clinical management of these patients is quite significant, and it usually includes initiation of amiodarone and/or digoxin in patients with AF, potential electrical cardioversion, or ablation in specific patients with indication, as well as initiation of anticoagulants in all patients, independent of AF and CHADS-VASc score, for potential intracardiac thrombus. Moreover, identification of patients with conduction disorders that could benefit from prophylactic pacemaker implantation and/or CRT as well as identification of patients with life-threatening ventricular arrythmias that could benefit from ICD could both increase the survival rates of these patients and improve their quality of life.
PubMed: 37623350
DOI: 10.3390/jcdd10080337 -
Biomedicines Apr 2024Drug-induced myopathies are a common cause of muscle pain, and the range of drugs that can cause muscle side effects is constantly expanding. In this article, the... (Review)
Review
Drug-induced myopathies are a common cause of muscle pain, and the range of drugs that can cause muscle side effects is constantly expanding. In this article, the authors comprehensively discuss the diagnostic and therapeutic process in patients with myalgia, and present the spectrum of drug-induced myopathies. The review provides a detailed analysis of the literature on the incidence of myopathy during treatment with hypolipemic drugs, beta-blockers, amiodarone, colchicine, glucocorticosteroids, antimalarials, cyclosporine, zidovudine, and checkpoint inhibitors, a group of drugs increasingly used in the treatment of malignancies. The article considers the clinical course of the different types of myopathies, their pathogenesis, histopathological features, and treatment methods of these disorders. The aim of this paper is to gather from the latest available literature up-to-date information on the course, pathophysiology, and therapeutic options of drug-induced myopathies, to systematize the knowledge of drug-induced myopathies and to draw the attention of internists to the fact that these clinical issues are an important therapeutic problem.
PubMed: 38790948
DOI: 10.3390/biomedicines12050987 -
Circulation. Arrhythmia and... Aug 2023Sotalol and dronedarone are both used for maintenance of sinus rhythm for patients with atrial fibrillation. However, while sotalol requires initial monitoring for QT...
BACKGROUND
Sotalol and dronedarone are both used for maintenance of sinus rhythm for patients with atrial fibrillation. However, while sotalol requires initial monitoring for QT prolongation and proarrhythmia, dronedarone does not. These treatments can be used in comparable patients, but their safety and effectiveness have not been compared head to head. Therefore, we retrospectively evaluated the effectiveness and safety using data from a large health care system.
METHODS
Using Veterans Health Administration data, we identified 11 296 antiarrhythmic drug-naive patients with atrial fibrillation prescribed dronedarone or sotalol in 2012 or later. We excluded patients with prior conduction disease, pacemakers or implantable cardioverter-defibrillators, ventricular arrhythmia, cancer, renal failure, liver disease, or heart failure. We used natural language processing to identify and compare baseline left ventricular ejection fraction between treatment arms. We used 1:1 propensity score matching, based on patient demographics, comorbidities, and medications, and Cox regression to compare strategies. To evaluate residual confounding, we performed falsification analysis with nonplausible outcomes.
RESULTS
The matched cohort comprised 6212 patients (3106 dronedarone and 3106 sotalol; mean [±SD] age, 71±10 years; 2.5% female; mean [±SD] CHADS-VASC, 2±1.3). The mean (±SD) left ventricular ejection fraction was 55±11 and 58±10 for dronedarone and sotalol users, correspondingly. Dronedarone, compared with sotalol, did not demonstrate a significant association with risk of cardiovascular hospitalization (hazard ratio, 1.03 [95% CI, 0.88-1.21]) or all-cause mortality (hazard ratio, 0.89 [95% CI, 0.68-1.16]). However, dronedarone was associated with significantly lower risk of ventricular proarrhythmic events (hazard ratio, 0.53 [95% CI, 0.38-0.74]) and symptomatic bradycardia (hazard ratio, 0.56 [95% CI, 0.37-0.87]). The primary findings were stable across sensitivity analyses. Falsification analyses were not significant.
CONCLUSIONS
Dronedarone, compared with sotalol, was associated with a lower risk of ventricular proarrhythmic events and conduction disorders while having no difference in risk of incident cardiovascular hospitalization and mortality. These observational data provide the basis for prospective efficacy and safety trials.
Topics: Female; Humans; Middle Aged; Aged; Aged, 80 and over; Male; Anti-Arrhythmia Agents; Dronedarone; Sotalol; Atrial Fibrillation; Retrospective Studies; Prospective Studies; Stroke Volume; Veterans; Ventricular Function, Left; Amiodarone
PubMed: 37485722
DOI: 10.1161/CIRCEP.123.011893