Assessing the Risk for Peripheral Neuropathy in Patients Treated With Dronedarone Compared With That in Other Antiarrhythmics

Abstract

Purpose

There are few data on the risk for peripheral neuropathy associated with dronedarone, a newer antiarrhythmic medicine. The objective of this study was to assess whether dronedarone is potentially associated with an increased risk for peripheral neuropathy compared with other antiarrhythmics, including amiodarone, sotalol, flecainide, and propafenone.

Methods

The MarketScan database was used for identifying patients who were at least 18 years of age, had atrial fibrillation or flutter, and had not been diagnosed with peripheral neuropathy in the 180-day period prior to or on the date of the first prescription of an antiarrhythmic between July 20, 2009, and December 31, 2011. Peripheral neuropathy that occurred during the treatment period for a study drug was ascertained using ICD-9-CM diagnostic codes. For each antiarrhythmic, the incidence rate of peripheral neuropathy was calculated. The adjusted hazard ratio (aHR) for peripheral neuropathy for dronedarone compared with another antiarrhythmic was obtained, with control for age, sex, diabetes mellitus status, and the presence of other comorbidities.

Findings

The study population included 106,933 patients treated with dronedarone (n = 12,989), amiodarone (n = 45,173), sotalol (n = 22,036), flecainide (n = 14,244), or propafenone (n = 12,491). The incidence rates (per 1000 person–years) of peripheral neuropathy were 1.33 for dronedarone, 2.38 for amiodarone, 1.20 for sotalol, 1.08 for flecainide, and 1.97 for propafenone. The aHRs for peripheral neuropathy for dronedarone relative to other drugs ranged from 0.53 (95% CI, 0.21–1.34) compared with propafenone, to 0.94 (95% CI, 0.38–2.30) compared with sotalol. A new-user analysis showed similar results.

Implications

The risks for peripheral neuropathy were not significantly different between dronedarone and other antiarrhythmics.

Introduction

Dronedarone is an antiarrhythmic medicine first approved in the United States in 2009 with indication to treat atrial fibrillation or atrial flutter.1, 2 Dronedarone demonstrates electrophysiologic characteristics of all of the 4 Vaughan-Williams classes of antiarrhythmics, and it mainly has a Class III effect and, to a limited extent, a Class I effect.¹

While peripheral neuropathy is considered a class effect (amiodarone-like effect), data from the dronedarone clinical program did not suggest it as a signal.¹ In the postmarketing period, it is of interest to further monitor the risk for peripheral neuropathy in clinical practice. In addition, there have been limited data in the literature on the relative risk for peripheral neuropathy in patients treated with antiarrhythmics. For amiodarone, a Class III antiarrhythmic, several case reports have described the development of peripheral neuropathy,3, 4, 5, 6, 7, 8 and a few case-series studies have examined the risk for peripheral neuropathy.9, 10 For flecainide, a Class I antiarrhythmic, there were 2 case reports of peripheral neuropathy.11, 12 However, there is a lack of population-based epidemiologic data examining the risk for peripheral neuropathy associated with antiarrhythmics, including dronedarone, which is a newer antiarrhythmic drug.²

Therefore, a retrospective cohort study was undertaken to examine whether dronedarone is potentially associated with a higher risk for peripheral neuropathy compared with other frequently prescribed major Class III and I antiarrhythmics, including amiodarone and sotalol (Class III antiarrhythmics), as well as flecainide and propafenone (Class I antiarrhythmics), using data from a large claims database.