Patients were followed for one year. Recurrence had occurred in The majority of recurrent events were symptomatic. Permanent discontinuation of the study drug following a treatment emergent adverse event occurred in 7. There were no cases of torsades de pointes during the month follow-up period. Dronedarone is a novel derivative of amiodarone designed to lower the adverse effects. There was one case of thrombosis 1.
In the non-European trial However, the populations of different studies vary considerably, which makes direct comparison impossible. There was no significant difference in the number of strokes reported as there were 4 strokes 0.
Stroke included cerebral-artery embolism, cerebrovascular accident, cerebral infarction, and transient ischemic attack. The efficacy and safety of dronedarone for the control of ventricular rate during AF ERATO study assessed the efficacy of dronedarone in the control of ventricular rate in patients with permanent AF. All patients had a history of symptomatic, permanent AF for minimum 6 months and resting ventricular rate of at least 80 beats per minute.
At day 14 the mean ventricular rate was measured to be During submaximal and maximal exercise the mean ventricular rate at day 14 was reduced by The serious cardiovascular events included 3 myocardial infarctions 1 in dronedarone vs 2 in placebo group and 1 heart failure in the dronedarone group and 1 unstable angina in the placebo group. The patients scheduled for cardioversion for AF or AFL were randomized to amiodarone or dronedarone mg twice daily , and the primary endpoint was the combined endpoint of recurrence of AF or premature discontinuation.
Recurrence of AF occurred for patients in the dronedarone group vs in the placebo group. The significant reduction in recurrence of AF by amiodarone is consistent with an indirect meta-analysis based on 4 studies of amiodarone and 4 studies of dronedarone. The antiarrhythmic trial with dronedarone in moderate to severe congestive heart failure evaluating morbidity decrease ANDROMEDA trial was a placebo-controlled multicenter study performed in patients admitted to hospital with moderate to severe heart failure and reduced left ventricular ejection fraction LVEF.
The study was planned to include patients and last for a minimum of 2 years. Every patient was treated for a minimum of 12 months. The primary end point was death from any cause or hospitalization for worsening heart failure. Secondary end points included all cause mortality and hospitalization for cardiovascular causes. After inclusion of patients in the dronedarone group and in the placebo group , the study was discontinued, when the Data, Safety and Management Board DSMB found that dronedarone was associated with a significantly higher mortality.
After a median 2-month follow-up, 25 patients in the dronedarone group and 12 patients in the control group had died, respectively. DSMB recommended that the study was stopped prematurely. Based on the small number of events it is difficult to know if this decision was correct. However, the increased mortality in the dronedarone was discovered at the first look at data, and repeated 1 month later. The steering committee discussed whether the advice of the DSMB should be followed, and decided to stop the study.
Subgroup analyses could not identify a specific group of patients to which the increased risk was confined, but the risk seemed to be associated with the sickest patients. In the dronedarone group an increased number had an increase in serum creatinine. It was suggested that dronedarone might decrease renal function but this suggestion was later rejected.
On the contrary, a study among 12 healthy males showed that dronedarone increases serum creatinine increasing tubular secretion without decreasing renal function. The study was done in patients with current or recent AF in order to show if dronedarone could affect mortality or morbidity. The primary end point was death or hospitalization for a cardiovascular reason.
The overall mortality figures were lower than expected, so the steering committee changed the inclusion criteria to enrich the risk profile of the overall study population.
With the revised criteria patients aged 75 years or older could be included whether or not they had any of the specified risk factors. Patients aged 70 years or older could be included if they had at least one of the risk factors. Patients younger than 70 years could no longer be included. Patients included in the study had an intermediate to high risk for stroke and other cardiovascular events. Mean followup period was 21 months. Exclusion criteria included permanent AF, severe heart failure NYHA class IV , unstable hemodynamic condition, bradycardia, planned major surgery and glomerular filtration rate of less than 10 mL per minute.
Hospitalization for cardiovascular reasons occurred in This difference in hospitalizations between the two groups was mainly caused by a reduction in the number of hospitalizations for AF. However, hospitalizations for AF were often related to other cardiovascular events ie, incompensation, stroke or myocardial infarction. Secondary endpoints included death from cardiovascular causes and any hospitalization due to cardiovascular events.
Death from cardiovascular reasons occurred in 63 2. Also, there were 26 deaths from cardiac arrhythmia 1. Any hospitalization due to any cardiovascular event or death from any cause occurred in From the published data it is difficult to see how many of these events were related to an effect on AF, and to see if dronedarone has additional effects not previously anticipated. In a post hoc analysis deaths were categorized into four subgroups: cardiac, arrhythmic; cardiac, nonarrhythmic; vascular, noncardiac; and nonvascular.
Information was then gathered from hospital reports, death reports and adverse event reports. The patients were followed for HR for all-cause mortality was 1. All findings were homogeneous across the 3 studies and similar to those observed in the overall population.
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