Major bleeding in patients with atrial fibrillation treated with apixaban versus warfarin in combination with amiodarone: the APIXAMIO study

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Drug utilisation

  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Retrospective registry-based observational study

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  APIXABAN

  WARFARIN

  AMIODARONE
• Medical condition to be studied:
  Atrial fibrillation
• Additional medical condition(s):
  Oral anticoagulation-associated bleedings

Population studied

• Short description of the study population:
  The study population included patients aged 18 years or older diagnosed with atrial fibrillation (AF) treated with amiodarone in combination with apixaban or warfarin between 1 June 2013 and 31 December 2018, identified from Swedish national registries.; Inclusion criteria: ; 1. Patients that have one or more AF (ICD-10 I48) diagnosis registered in the National Patient Register; 2. Patients ≥ 18 years; 3. Patients who had a filled prescription for amiodarone and apixaban or warfarin during the identification period; ; Exclusion criteria:; 1. Patients with valvular AF (defined as patients with mechanical heart valves (Z952) implanted before index, or with a diagnosis of mitral stenosis before and including index date (I342, I050, I052, Q232).; 2. Patients with an acute venous thromboembolism 6 months period before and including the index date (I26, I801, I802, I803, I808, I809, I822, I823, I828, I829, O223, O871, O882).; 3. Patients with diagnosis or procedure-code for hip/knee replacement surgery within 6 weeks before and including index date (NFB, NFC, NGB, NGC, NFG, NGG).; 4. Diagnosis codes indicating pregnancy 9 months before and including index date (A34, O00-O99, Z33, Z34, Z35, Z36, Z37, Z39, Z640, Z641).; 5. Patients dispensing simultaneously more than one OAC (ATC code B01AA03, B01AE07, B01AF01, B01AF02, B01AF03) during the identification period.
• 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:
  Patients with atrial fibrillation
• Estimated number of subjects:
  10000

Study design details

• Main study objective:
  To describe the clinical characteristics in patients with AF treated with amiodarone in combination with apixaban or warfarin. To compare the occurrence of major bleedings in patients with atrial fibrillation treated with the combination of apixaban + amiodarone versus the combination of warfarin + amiodarone.
• Outcomes:
  If the feasibility analysis after assessing the descriptive data are robust and valid enough to conduct a comparative safety analysis between apixaban and warfarin in combination with amiodarone in terms of bleeding the primary outcome will be: • To compare the occurrence of major bleeding in patients treated with amiodarone in combination with apixaban versus warfarin., Intracranial bleeding Gastro-intestinal bleeding Other bleedings leading to hospitalization
• Data analysis plan:
  Kaplan-Meier estimates with accompanying at risk tables for the treatment analysis will be plotted to illustrate all outcomes with regard to apixaban+amiodarone versus warfarin+amiodarone, before and after the propensity score matching. Matched cohorts will be compared with regard to outcome events using Cox regression analysis and with adjustments for relevant covariates.