Dronedarone: A Safety Comparison to Amiodarone

Abstract

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.

A multilayer three-dimensional superconducting nanowire photon detector

“…The characteristics of nanowire detectors have been studied in depth elsewhere [9,10,11,12,14,15,16,17,19]. We will not repeat this fundamental work but will instead characterize the unique qualities of this device.…”

“…The current density will increase as it passes around these corners, in what is known as current crowding. Current crowding in superconducting nanowires has been studied by Clem and Berggren [17] for several bend geometries. They discuss an optimal 90…”

“…Thus one possible change to the shape of the bridge could be rounding the joint between the middle and detection, shown in figure (1). This would turn the bridges into elongated arches and reduce the current crowding at the interface [17]. The pixel bridge will be less susceptible to current crowding than standard meanders as there are no in plan 90…”

“…To maintain the superconductivity the critical current will be reduced by these effects. This reduces the current density in the rest of the unconstricted wire which has the effect of reducing the quantum efficiency η [17,19]. Also the narrowing of the nanowire may also effect the kinetic inductance mentioned above and in [14].…”

“…First the radius of curvature can not become infinitely small at the center. Setting aside fabrication issues, there is a limit set by current crowding that will reduce the overall efficiency of the wire due to sharp curves [17]. This means there is a finite sized hole in the center of the Spiral Meander, which we use to place the sinks.…”