Concomitant use of dronedarone and digoxin (or statins) and the risk of digitalis intoxication (or rhabdomyolysis and myopathy)-- a post-marketing cohort study using the US Clinformatics DataMart® (formerly LabRx®) database

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

• Anatomical Therapeutic Chemical (ATC) code:
  (C01AA05) digoxin

  digoxin

  (C01BD07) dronedarone

  dronedarone

  (C10AA) HMG CoA reductase inhibitors

  HMG CoA reductase inhibitors
• Medical condition to be studied:
  Atrial fibrillation

Population studied

• Short description of the study population:
  The study population consisted of 2 cohorts (digoxin and statin cohorts) of patients identified from the Clinformatics DataMart® database who were at least 18 years old, had a diagnosis of atrial fibrillation (AF) or flutter (AFL), and filled a prescription of digoxin or statins between July 20, 2009 (the launch date of dronedarone in the US) and March 31, 2016. Statins of interest included atorvastatin, simvastatin, lovastatin, and pravastatin. Fluvastatin and rosuvastatin were not considered for potential interactions with dronedarone because they are not metabolized or only weakly metabolized by CYP3A4 and are not P-gP substrates. The cohort entry date was the date on which the first prescription of digoxin or statins was dispensed. Excluded from the cohort were the patients with the following conditions on the cohort entry date: (1) less than 6 months of enrolment period in the managed care organization (United Healthcare), and (2) a diagnosis of the outcome of interest within six months prior to the cohort entry date.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 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:
  32459

Study design details

• Main study objective:
  To evaluate if the concomitant use of dronedarone increases the risk of dose-related digitalis intoxication in digoxin users and the risk of rhabdomyolysis and myopathy in statin users.
• Outcomes:
  Digitalis intoxication, Rhabdomyolysis and myopthay
• Data analysis plan:
  Incidence rates of outcomes the concomitant use cohort and the single-drug cohort (digoxin or statins) were calculated. Adjusted hazard ratios for outcomes comparing concomitant use to the single-drug use were calculated.