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Medicine Apr 2023There is no evidence that antiarrhythmic drugs can improve long-term survival or survival with favorable neurological outcomes in cardiac arrest patients. We did this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is no evidence that antiarrhythmic drugs can improve long-term survival or survival with favorable neurological outcomes in cardiac arrest patients. We did this network meta-analysis to comprehensively compare the efficacy of various antiarrhythmic drugs for cardiac arrest patients.
METHODS
We searched studies from inception until Nov 11, 2022 through PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, and Wanfang database. All studies comparing different antiarrhythmic drugs for cardiac arrest were included in this meta-analysis. Outcomes were survival to hospital discharge in cardiac arrest, survival to hospital admission/24 h and favorable neurological outcome. This network meta-analysis was performed by R software.
RESULTS
Finally, a total of 9 studies (10,980 patients) were finally included in this network meta-analysis. Amiodarone (odd ratio [OR] 2.28, 95% credibility interval [CrI] 1.61-3.27) and lidocaine (OR 1.53, 95% CrI 1.05-2.25) was superior than placebo in terms of the survival to hospital admission/24 h with statistically significant. Amiodarone (OR 2.19, 95% CrI 1.54-3.14) and lidocaine (OR 1.58, 95% CrI 1.09-2.32) was superior than placebo in terms of the survival to hospital discharge with statistically significant. Amiodarone (OR 2.43, 95% CrI 1.61-3.68) and lidocaine (OR 1.62, 95% CrI 1.04-2.53) was superior than placebo in terms of the favorable neurological outcome with statistically significant. The surface under the cumulative ranking (SUCRA) shows that amiodarone ranked first (SUCRA, 99.6%), lidocaine ranked second (SUCRA, 49.6%), placebo ranked the last (SUCRA, 0.86%). Inverted funnel plot is essentially symmetrical, it is possible that this study has a small sample effect or a small publication bias.
CONCLUSIONS
Amiodarone had the best effect on both survival to hospital admission, discharge and more favorable neurological outcome. Thus, amiodarone should be listed as first line drug for cardiac arrest. However, the quality of available evidence limits the formation of powerful conclusions regarding the comparative efficacy or safety of amiodarone or lidocaine used to treat cardiac arrest. Higher-quality randomized controlled trials are required for further research in future.
Topics: Humans; Amiodarone; Lidocaine; Anti-Arrhythmia Agents; Network Meta-Analysis; Heart Arrest
PubMed: 37058064
DOI: 10.1097/MD.0000000000033195 -
British Journal of Clinical Pharmacology May 2009To determine if amiodarone, highly lipophilic, accumulates in excess with respect to dose in fat tissue during long-term administration, and study if plasma and fat...
AIMS
To determine if amiodarone, highly lipophilic, accumulates in excess with respect to dose in fat tissue during long-term administration, and study if plasma and fat tissue concentrations are correlated with adverse effects.
METHODS
Trough concentrations of amiodarone and N-desethyl-amiodarone were measured simultaneously in plasma and fat tissue, in 30 consecutive patients treated with amiodarone for 3 months to 12 years. Subcutaneous adipose tissue was obtained by needle aspiration from lumbar and abdominal areas. Concentrations were measured by liquid chromatography-tandem mass spectrometry.
RESULTS
Plasma levels of amiodarone and N-desethyl-amiodarone were significantly correlated with daily maintenance doses (R= 0.52, P= 0.003). Amiodarone concentrations in fat tissue were four to 226 times (mean 55) higher than in plasma, and well correlated with plasma levels (R= 0.68, P < 0.001). Concentrations of amiodarone and N-desethyl-amiodarone in adipose tissue did not significantly increase with higher total cumulated doses or longer treatment duration. Nine of 12 patients who had received amiodarone for > or =2 years developed clinically important adverse effects, predominantly hypothyroidism (n= 6), compared with two of 18 patients treated for less time (relative risk 6.75; 95% confidence interval 1.8, 26). The incidence of those adverse effects was not significantly associated with amiodarone concentrations, whether in plasma or in adipose tissue.
CONCLUSIONS
We found no evidence of excessive or unexpected accumulation of amiodarone in fat tissue on long-term administration. Late amiodarone adverse effects, particularly hypothyroidism, are associated with longer exposure times, but do not seem to be explained by higher concentrations in plasma or in fat tissue.
Topics: Adipose Tissue; Adult; Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Female; Heart Diseases; Humans; Male; Middle Aged; Plasma; Risk Factors
PubMed: 19552745
DOI: 10.1111/j.1365-2125.2009.03381.x -
Physiological Research Dec 2022Amiodarone seems to exhibit some antiviral activity in the disease caused by SARS-CoV-2. Here we have examined the SARS-CoV-2 disease course in the entire population of...
Amiodarone seems to exhibit some antiviral activity in the disease caused by SARS-CoV-2. Here we have examined the SARS-CoV-2 disease course in the entire population of the Czech Republic and compared it with the course of the disease in patients treated with amiodarone in two major Prague's hospitals. In the whole population of the Czech Republic SARS-CoV-2 infected 1665070 persons (15.6 %) out of 10694000 (100 %) between 1 April 2020 and 30 June 2021. In the same time period only 35 patients (3.4 %) treated with amiodarone were infected with SARS-CoV-2 virus out of 1032 patients (100 %) who received amiodarone. It appears that amiodarone can prevent SARS-CoV-2 virus infection by multiple mechanisms. In in-vitro experiments it exhibits SARS-CoV-2 virus replication inhibitions. Due to its anti-inflammatory and antioxidant properties, it may have beneficial effect on the complications caused by SARS-CoV-2 as well. Additionally, inorganic iodine released from amiodarone can be converted to hypoiodite (IO-), which has antiviral and antibacterial activity, and thus can affect the life cycle of the virus.
Topics: Humans; COVID-19; Antiviral Agents; SARS-CoV-2; Amiodarone; Anti-Bacterial Agents
PubMed: 36426888
DOI: 10.33549/physiolres.934974 -
Cardiovascular Therapeutics 2010Atrial fibrillation (AF) is the most common sustained arrhythmia, affecting more than 2.2 million Americans. ACC/AHA/ESC guidelines for the management of patients with... (Review)
Review
Atrial fibrillation (AF) is the most common sustained arrhythmia, affecting more than 2.2 million Americans. ACC/AHA/ESC guidelines for the management of patients with AF recommend amiodarone for maintaining sinus rhythm. Dronedarone is a derivative of amiodarone indicated for the treatment of AF. To provide an overview of dronedarone with a focus on the phase III trials and discuss unresolved questions of dronedarone. A literature search was conducted via the PubMed database using the keyword "dronedarone." Search was limited to human trials in english. The FDA website was searched for briefing documents and subcommittee meetings on dronedarone. Clinicaltrials.gov was searched with the keyword dronedarone for upcoming or unpublished clinical trials. Five phase III trials are available for dronedarone: ANDROMEDA, EURIDIS/ADONIS, ATHENA, ERATO, and DIONYSIS. EURIDIS/ADONIS and ATHENA demonstrated a reduction AF recurrence with dronedarone compared to placebo. The ANDROMEDA trial recruited patients with recent hospitalization for heart failure and was terminated due to an excess of deaths in the dronedarone group. The DIONYSIS trial was a comparative effectiveness trial that demonstrated less efficacy for dronedarone but improved tolerability compared to amiodarone. Dronedarone represents an option in the management of AF in select patients. Dronedarone is not appropriate in patients with recently decompensated heart failure or those treated with strong CYP3A4 inhibitors or medications prolonging the QT interval. Dronedarone appears to have improved tolerability at the expense of decreased efficacy when compared to amiodarone. Questions remain on the long-term safety, use in patients with heart failure, retreatment after dronedarone or amiodarone failure, and comparative efficacy with a rate control strategy.
Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Dronedarone; Drug Interactions; Evidence-Based Medicine; Humans; Patient Selection; Risk Assessment; Treatment Outcome
PubMed: 20074258
DOI: 10.1111/j.1755-5922.2009.00112.x -
Frontiers in Cellular and Infection... 2022Chagas disease (CD), a neglected tropical disease caused by the protozoan parasite , is an important public health problem mainly in Latin America, leading to...
Chagas disease (CD), a neglected tropical disease caused by the protozoan parasite , is an important public health problem mainly in Latin America, leading to approximately 12,000 annual deaths. Current etiological treatment for CD is limited to two nitro compounds, benznidazole (Bz) and nifurtimox (Nif), both presenting relevant limitations. Different approaches have been employed to establish more effective and safer schemes to treat infection, mostly based on drug repurposing and combination therapies. Amiodarone (AMD), an antiarrhythmic medicament of choice for patients with the chronic cardiac form of CD, is also recognized as a trypanocidal agent. Therefore, our aim is to investigate the combined treatment Bz + AMD on trypomastigote viability, control of intracellular form proliferation, and recovery of the infection-induced cytoskeleton alterations in cardiac cells. The combination of Bz + AMD did not improve the direct trypanocidal effect of AMD on the infective blood trypomastigote and replicative intracellular forms of the parasite. Otherwise, the treatment of -infected cardiac cells with Bz plus AMD attenuated the infection-triggered cytoskeleton damage of host cells and the cytotoxic effects of AMD. Thus, the combined treatment Bz + AMD may favor parasite control and hamper tissue damage.
Topics: Amiodarone; Chagas Disease; Cytoskeleton; Humans; Nitroimidazoles; Trypanocidal Agents; Trypanosoma cruzi
PubMed: 36093188
DOI: 10.3389/fcimb.2022.975931 -
Microbiology Spectrum Feb 2022Chagas disease (CD), caused by Trypanosoma cruzi, affects approximately 6 to 7 million people in Latin America, with cardiomyopathy being the clinical manifestation most...
Chagas disease (CD), caused by Trypanosoma cruzi, affects approximately 6 to 7 million people in Latin America, with cardiomyopathy being the clinical manifestation most commonly associated with patient death during the acute phase. The etiological treatment of CD is restricted to benznidazole (Bz) and nifurtimox (Nif), which involve long periods of administration, frequent side effects, and low efficacy in the chronic phase. Thus, combined therapies emerge as an important tool in the treatment of CD, allowing the reduction of Bz dose and treatment duration. In this sense, amiodarone (AMD), the most efficient antiarrhythmic drug currently available and prescribed to CD patients, is a potential candidate for combined treatment due to its known trypanocidal activity. However, the efficacy of AMD during the acute phase of CD and its interaction with Bz or Nif are still unknown. In the present study, using a well-established murine model of the acute phase of CD, we observed that the Bz/AMD combination was more effective in reducing the peak parasitemia than both monotherapy treatments. Additionally, the Bz/AMD combination reduced (i) interleukin-6 (IL-6) levels in cardiac tissue, (ii) P-wave duration, and (iii) frequency of arrhythmia in infected animals and (iv) restored gap junction integrity in cardiac tissue. Therefore, our study validates AMD as a promising candidate for combined therapy with Bz, reinforcing the strategy of combined therapy for CD. Chagas disease affects approximately 6 to 7 million people worldwide, with cardiomyopathy being the clinical manifestation that most commonly leads to patient death. The etiological treatment of Chagas disease is limited to drugs (benznidazole and nifurtimox) with relatively high toxicity and therapeutic failures. In this sense, amiodarone, the most effective currently available antiarrhythmic drug prescribed to patients with Chagas disease, is a potential candidate for combined treatment due to its known trypanocidal effect. In the present study, we show that combined treatment with benznidazole and amiodarone improves the trypanocidal effect and reduces cardiac damage in acutely T. cruzi-infected mice.
Topics: Amiodarone; Animals; Chagas Disease; Disease Models, Animal; Drug Therapy, Combination; Heart; Heart Diseases; Heart Function Tests; Humans; Male; Mice; Nitroimidazoles; Parasitemia; Trypanosoma cruzi
PubMed: 35138142
DOI: 10.1128/spectrum.01852-21 -
Journal of the American College of... May 1987Because the value of monitoring amiodarone plasma concentrations remains undefined, this study was performed to evaluate its role during the management of patients...
Because the value of monitoring amiodarone plasma concentrations remains undefined, this study was performed to evaluate its role during the management of patients receiving amiodarone. The early electrophysiologic effects of amiodarone were assessed in 40 consecutive patients with coronary artery disease and sustained ventricular tachycardia or fibrillation who underwent electrophysiologic studies and measurement of amiodarone plasma concentration before and 29 +/- 15 (mean +/- SD) days after initiation of therapy. Amiodarone and desethylamiodarone plasma levels did not correlate with changes in either sinus cycle length, QTc interval, ventricular effective refractory period, AH and HV intervals or ventricular tachycardia cycle length. Amiodarone and desethylamiodarone plasma concentrations and the effects of the drug on conduction intervals or right ventricular effective refractory periods were not related to suppression of arrhythmia induction by ventricular stimulation after 1 month of therapy. The relation between amiodarone plasma concentrations and both toxicity and efficacy during long-term therapy were prospectively assessed in a larger series of 114 consecutive patients with either symptomatic supraventricular or ventricular arrhythmias who were followed up on long-term amiodarone therapy for 26 +/- 15 months. Sixty-three patients (55%) had one or more adverse effects attributed to amiodarone. By life-table analysis, 40, 69 and 80% of patients had experienced an adverse reaction after 1, 2 and 3 years of therapy, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Coronary Disease; Dose-Response Relationship, Drug; Electrocardiography; Electrophoresis; Female; Humans; Male; Middle Aged; Osmolar Concentration; Recurrence
PubMed: 3571754
DOI: 10.1016/s0735-1097(87)80320-0 -
Journal of the American College of... Nov 1992
Topics: Amiodarone; Drug Evaluation; Humans; Myocardial Infarction
PubMed: 1401603
DOI: 10.1016/0735-1097(92)90358-t -
JACC. Clinical Electrophysiology Aug 2022
Topics: Amiodarone; Arrhythmias, Cardiac; Drug-Related Side Effects and Adverse Reactions; Humans
PubMed: 35981796
DOI: 10.1016/j.jacep.2022.07.002 -
European Review For Medical and... Dec 2018The aim of the study was to examine the safety and efficacy of dronedarone in patients with a history of atrial fibrillation and amiodarone-induced hyperthyroidism.
OBJECTIVE
The aim of the study was to examine the safety and efficacy of dronedarone in patients with a history of atrial fibrillation and amiodarone-induced hyperthyroidism.
PATIENTS AND METHODS
We conducted a prospective study to evaluate the use of amiodarone and dronedarone in 124 patients with a history of paroxysmal atrial fibrillation who had no additional structural heart disease. All patients received amiodarone 200 mg qd. Out of 124 patients, 56 (45%) switched to dronedarone 400 mg bid due to amiodarone-induced hyperthyroidism and the remaining 68 patients (55%), with normal thyroid function, continued to receive amiodarone. The follow-up period was 12 months, and the patients were regularly monitored.
RESULTS
The primary outcome after 6 months dronedarone and amiodarone group was 56 and 68, including 38 (68%) and 54 (79.4%) (Odds ratio [OR] = 1.17, 95% confidence interval [95% CI] = 0.68-2.02) patients with sinus rhythm (SR) and 18 (32.14%) and 14 (28.6%) (odds ratio [OR] = 0.64, confidence interval [95% CI] = 0.29-1.40) patients with atrial fibrillation (AF). The secondary outcome after 12 months showed significant difference in thyroid function in the dronedarone group. Out of 46 patients, 24 (56.18%) patients reduced hyperthyroidism compared to the amiodarone group; out of 68, 6 (8.9%) patients were observed to have hyperthyroidism. At 12 months, there were 24 (43%) and 22 (62%) (odds ratio [OR] = 0.75, confidence interval [95% CI] = 0.38-1.49) patients with SR, and 32 (57%) and 26 (38%) (odds ratio [OR] = 0.67, confidence interval [95% CI] = 0.36-1.25) patients with AF.
CONCLUSIONS
In our study, dronedarone appears to be a good therapeutic option in the treatment of atrial fibrillation in patients with amiodarone-induced hyperthyroidism. However, long-term studies are needed to estimate the efficacy and toxicity of both drugs.
Topics: Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Dronedarone; Female; Humans; Hyperthyroidism; Male; Middle Aged; Prospective Studies
PubMed: 30556893
DOI: 10.26355/eurrev_201812_16551