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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dronedarone. Dronedarone is a benzofuran derivative pharmacologically related to amiodarone but without the iodine moiety. It is designed for the treatment of atrial fibrillation and atrial flutter. Historically, amiodarone has proved most effective in maintaining sinus rhythm and has been used safely in patients with advanced heart failure. However, its use has been limited by cumulative and often irreversible organ toxicity, especially in younger patients. Dronedarone was developed in an effort to provide equivalent efficacy and safety with less toxicity. Dronedarone has proved efficacious without toxic or proarrhythmic effects and has minimal side effects, but remaining concerns exist regarding its use in patients with advanced heart failure.
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PMID:Dronedarone: a new treatment for atrial fibrillation. 1870 18

Amiodarone and dronedarone are two clinically important benzofuran derivatives. Amiodarone has been used widely for treating resistant tachyarrhythmias in the past three decades. However amiodarone and its main metabolically active metabolite desethylamiodarone can adversely affect many organs, including the thyroid gland. Amiodarone-induced thyroid disorders are common and often present as a management challenge for endocrinologists. The pathogenesis of amiodarone-induced thyroid dysfunction is complex but the inherent effects of the drug itself as well as its high iodine content appear to play a central role. The non-iodinated dronedarone also exhibits anti-arrhythmic properties but appears to be less toxic to the thyroid. This review describes the biochemistry of benzofuran derivatives, including their pharmacology and the physiology necessary for understanding the cellular mechanisms involved in their actions. The known effects of these compounds on thyroid action are described. Recommendations for management of amiodarone-induced hypothyroidism and thyrotoxicosis are suggested. Dronedarone appears to be an alternative but less-effective anti-arrhythmic agent and it does not have adverse effects on thyroid function. It may have a future role as an alternative agent in patients being considered for amiodarone therapy especially those at high risk of developing thyroid dysfunction but not in severe heart failure.
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PMID:Benzofuran derivatives and the thyroid. 1872 7

Treatment of patients with both atrial fibrillation and heart failure remains uneasy. In theory maintenance of sinus rhythm is desirable but the only pharmacological intervention able to do it safely is amiodarone. A trial of strategy randomisation, restoration of sinus rhythm or slowing of atrial fibrillation, has been done in patients with both atrial fibrillation and heart failure. This trial, named AF-CHF has shown neutral results, the 2 strategies, rhythm control or simple rate control were similar in terms of mortality. Dronedarone is an innovative drug bringing new possibilities in the treatment of atrial fibrillation but it is contra-indicated in case of severe heart failure. Another possible approach is that of non pharmacological techniques. Sinus rhythm maintenance may be obtained by pulmonary vein isolation. The other possibility is the ablation of atrio-ventricular node with implantation of a pacemaker, technique which is reserved to selected patients.
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PMID:[Treatment of atrial fibrillation in heart failure]. 1966 5

Amiodarone is the most effective antiarrhythmic drug for maintaining sinus rhythm for patients with atrial fibrillation. Extra-cardiac side effects have been a limiting factor, especially during chronic use, and may offset its benefits. Dronedarone is a noniodinated benzofuran derivative of amiodarone that has been developed for the treatment of atrial fibrillation and atrial flutter. Similar to amiodarone, dronedarone is a potent blocker of multiple ion currents, including the rapidly activating delayed-rectifier potassium current, the slowly activating delayed-rectifier potassium current, the inward rectifier potassium current, the acetylcholine activated potassium current, peak sodium current, and L-type calcium current, and exhibits antiadrenergic effects. It has been studied for maintenance of sinus rhythm and control of ventricular response during episodes of atrial fibrillation. Dronedarone reduces mortality and morbidity in patients with high-risk atrial fibrillation, but may be unsafe in those with severe heart failure. This article will review evidence of safety and effectiveness of dronedarone in patients with atrial fibrillation.
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PMID:Dronedarone. 1968 70

In the armamentarium for rhythm control, amiodarone has been a mainstay of therapy for the management of atrial fibrillation (AF). Although amiodarone has shown to be effective in maintaining sinus rhythm, it has many extracardiac adverse effects. Dronedarone, a benzofuran amiodarone derivative, is structurally modified to reduce toxicities often associated with chronic amiodarone therapy. With the addition of a methylsulfonyl group, dronedarone is less lipophilic, has lower tissue accumulation, and a much shorter serum half-life of 24 hours compared with amiodarone. Dronedarone is also designed without the iodine moieties that are responsible for thyroid dysfunctions associated with amiodarone. Similar to amiodarone, dronedarone exhibits electrophysiologic characteristics of all 4 Vaughan Williams classifications. Phase III clinical trials have shown dronedarone to be effective at reducing ventricular rate, reducing recurrence of AF, and reducing cardiovascular morbidity and mortality in patients with AF or atrial flutter (AFL). However, dronedarone was associated with increased mortality in one study that included patients with severe heart failure (HL) and left ventricular dysfunction. Overall, dronedarone appears to be well tolerated. The most common side effects are gastrointestinal in nature and include nausea, vomiting, and diarrhea. Because of its more favorable adverse effect profile, dronedarone is likely to be a useful addition to the therapeutic management of AF. However, further comparative studies with amiodarone are needed to define dronedarone's place in therapy more clearly.
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PMID:Dronedarone: a new antiarrhythmic agent for the treatment of atrial fibrillation. 1969 Apr 74

The maintenance of sinus rhythm in patients with Atrial Fibrillation (AF) is difficult and is complicated by adverse drug reactions of antiarrhythmic drugs or the adverse events related with ablation procedures. Amiodarone can be used for preventing AF recurrence; but it has the risk of serious toxicities secondary to its iodinated nature. Dronedarone, an amiodarone analogue without iodine, has been shown to decrease the frequency of AF recurrence and to provide heart rate control during AF recurrence. Dronedarone is a benzofuran derivative; specifically N-[2-Butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5-benzofuranyl]methane-sulfonamide and its production process has been patented. In the ATHENA trial, dronedarone therapy was associated with a significant reduction in the combined primary endpoint of death from any cause or hospitalization due to cardiovascular causes. However, dronedarone has been noted to increase cardiovascular mortality among patients with advanced congestive heart failure (NYHA class III and IV). On March 18, 2009, the Cardiovascular and Renal Drugs Advisory Committee of the Food and Drug Administration (FDA) approved dronedarone for an indication of atrial fibrillation suppression, with a warning against its use in patients with NYHA class III and IV heart failure or recently decompensated heart failure.
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PMID:Dronedarone--a new alternative for management of atrial fibrillation. 2000 29

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.
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PMID:Dronedarone: current evidence and future questions. 2007 58

Dronedarone is an oral Class III antiarrhythmic agent which was recently approved by the US Food and Drug Administration for use in nonpermanent atrial fibrillation. Structurally similar to amiodarone, dronedarone is a benzofuran derivative but it lacks the iodine moiety attached to amiodarone. Based upon the investigational clinical trials to date, it appears that dronedarone has an established efficacy when compared to placebo along with exhibiting a minimal adverse effect profile. The efficacy of dronedarone will need to be further evaluated in comparison trials with established antiarrhythmics for atrial fibrillation. The adverse profile of dronedarone appears to be substantially safer in comparison to amiodarone, although there is still little data available. The adverse effect profile of amiodarone necessitates close and extensive monitoring. Although a risk of pulmonary toxicity was identified in animals, long term studies in humans are needed to determine the significance of this adverse effect with dronedarone. One noted effect of dronedarone is an isolated increase in serum creatinine levels, and the clinical relevance of this effect needs further evaluation. Based on supporting evidence, the use of dronedarone is contraindicated in advanced or decompensated heart failure. Some clinically significant dronedarone drug interactions have been identified. Although the potential differences between dronedarone and amiodarone have been evaluated there have been no direct comparison trials published to date. This article reviews the chemistry, antiarrhythmic effects, pharmacokinetics, efficacy, adverse effects and drug interactions of dronedarone.
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PMID:Dronedarone: a safety comparison to amiodarone. 2021 Jul 34

Atrial fibrillation (AF) is a common arrhythmia, with a prevalence ranging from 0.1% to 9.0% at different ages, and is associated with increased cardiovascular events and mortality. A significant increase in the prevalence of the disease is expected to occur in the coming years as a consequence of the aging of the population and advances in the management of coronary artery disease and heart failure. Effective rhythm control may be difficult to obtain in a significant proportion of patients with AF. The limited efficacy and the possible adverse effects of antiarrhythmic drugs has led researchers to focus their attention on new molecules, in a search of compounds with antiarrhythmic efficacy and a more favourable safety profile. Among several new drugs developed for the management of AF, dronedarone, a benzofuran derivative that shares many of the antiarrhythmic properties of amiodarone, but with a more favourable safety profile, seems particularly promising. The drug is noniodinated, has less lipophilicity, reaches therapeutic concentrations over a shorter period of time and has lower tissue accumulation. Dronedarone, similarly to amiodarone, exhibits electrophysiologic characteristics of all 4 Vaughan Williams classes. Clinical studies have shown that dronedarone effectively reduces ventricular rate, may prevent or delay the recurrence of AF, and may reduce cardiovascular morbidity and mortality in patients with AF or atrial flutter. The drug has an overall good safety profile, in particular with low pulmonary and thyroid toxicity. An important exception is represented by patients with unstable haemodynamic conditions, in which the use of dronedarone has been found to be associated with an increase in mortality. Dronedarone has been recently approved for clinical use by the Food and Drug Administration and by the European Medicines Agency. Further results from trials and clinical use will better define the efficacy and safety profile of dronedarone in AF compared with other antiarrhythmic drugs and its role in the management of patients with AF.
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PMID:Dronedarone: an emerging therapy for atrial fibrillation. 2041 70

Dronedarone, a new Class III antiarrhythmic agent, has now been approved by the US Food and Drug Administration for use in patients with atrial fibrillation or atrial flutter. Approval came in March 2009 due to the positive results of the ATHENA trial showing significant reductions in all-cause mortality and cardiovascular hospitalization with dronedarone use. A post hoc analysis of the ATHENA data also suggested a decrease in stroke risk with this agent. However, due to safety concerns in the heart failure population in the earlier ANDROMEDA trial, dronedarone is not recommended for patients with an ejection fraction <35% and recent decompensated heart failure. Dronedarone is an amiodarone analog with multichannel blocking electrophysiologic properties similar to those of amiodarone, but several structural differences. Dronedarone's lack of the iodine moiety reduces its potential for thyroid and pulmonary toxicity. Preliminary data from the DIONYSOS trial, and an indirect meta-analysis comparing amiodarone with dronedarone, showed amiodarone to be more effective in maintaining sinus rhythm, while dronedarone was associated with fewer adverse effects resulting in early termination of the drug. Dronedarone is the first antiarrhythmic drug for the treatment of atrial fibrillation and atrial flutter shown to reduce cardiovascular hospitalizations. In patients with structural heart disease who have an ejection fraction >35% and no recent decompensated heart failure, dronedarone should be considered earlier than amiodarone in the treatment algorithm.
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PMID:Dronedarone for the treatment of atrial fibrillation and atrial flutter: approval and efficacy. 2073 68


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