Serious Liver Injury and Interstitial Lung Disease Occurrences in Patients Diagnosed with Atrial Fibrillation Treated with Selected Antiarrhythmics

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  MULTAQ
• Study drug International non-proprietary name (INN) or common name:
  DRONEDARONE
• Anatomical Therapeutic Chemical (ATC) code:
  (C01BD07) dronedarone

  dronedarone
• Medical condition to be studied:
  Atrial fibrillation

Population studied

• Short description of the study population:
  The study population will be comprised of patients treated for newly occurring atrial fibrillation or flutter (AF/AFL), including those who are treated with anti-arrhythmic drugs (dronedarone, amiodarone, sotalol, flecainide, dofetilide) as well as a population not treated with these anti-arrhythmic drugs (but could be treated with rate control drugs e.g., digoxin or beta blockers).; ; Overall patient inclusion criteria were:; • 365 days of continuous eligibility in the health plan prior to and including the Index Date;; • A new prescription for any one of the following six anti-arrhythmic agents: dronedarone, amiodarone, sotalol, flecainide, dofetilide, or propafenone, dispensed between 20 July 2009 (the dronedarone launch date in the US) and 31 March 2014. The first of these drugs of interest dispensed during the patient selection period determined a patient’s study cohort assignment and was referred to as the patient’s Index Drug. The date on which that first study medication was dispensed was defined as the patient’s Index Date, and the 365 days prior to and including the patient’s Index Date defined their baseline period;; • Diagnosed with atrial fibrillation (AF, ICD-9-CM diagnosis code 427.31) during the baseline period;; • No use of the Index Drug during the baseline period. Use of non-index study drugs during the baseline period was allowed;; • Patient aged 18 years or older as of their Index Date.; ; Overall patient exclusion criteria were:; • Unknown gender;; • Index Drug use during the baseline period;; • Multiple study drugs on the Index Date;; • Less than 365 days of continuous eligibility in the health plan prior to and including the Index Date;; • Absence of a diagnosis of AF during the baseline period;; • A diagnosis of cancer, organ transplant, or HIV during the baseline period;; • Women who were pregnant during the 280 days prior to and including the Index Date, or became pregnant during the 280 days following the Index Date, or; • Date of death preceding Index Date
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Atrial fibrillation patients
• Estimated number of subjects:
  80524

Study design details

• Main study objective:
  1. To count the number of new users of dronedarone and comparators identified from administrative claims databases and electronic health records (EHR) on a quarterly basis.; 2. To identify the number of serious liver injury occurrences among new users of dronedarone and comparators.
• Outcomes:
  Serious liver injury/disease, interstitial lung disease
• Data analysis plan:
  Tables summarizing baseline characteristics of patients in each of the cohorts were generated. Patients in the dronedarone cohort and those in the other anti-arrhythmic drug cohorts were matched on the propensity of being treated with the drug of interest. The number of patient-years of observation, the number of incident events, raw event rate with its 95% confidence interval, and the p-value for the comparison of event rates between the comparator drugs and dronedarone were calculated. In order to compare rates of outcome events over time, if enough events were identified separate Cox Proportional Hazards regression analyses were conducted for each outcome (i.e. SLD and ILD). Hazard ratios, with their 95% confidence intervals and p-values, for each comparator drug relative to dronedarone were reported, if data warranted. Kaplan-Meier curves were generated to display the risk of each out.

Documents

Study results

DRONEC05917 Study report_Part 1

Study report

DRONEC05917 Study report_Part 1.pdf

DRONEC05917 Study report_Part 2.pdf