Post-Authorization Safety Study (PASS): Investigating the occurrence of major bleedings in real life, in patients with atrial fibrillation (AF) treated with the combination of apixaban and dronedarone compared against patients on warfarin and dronedarone

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

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

  DRONEDARONE

  WARFARIN
• Medical condition to be studied:
  Atrial fibrillation

Population studied

• Short description of the study population:
  Patients with Atrial fibrillation (AF) treated with the combination of apixaban and dronedarone or the combination of warfarin and dronedarone.; Patients with following criteria were included:; 1. Have ≥1 AF diagnosis registered in the Patient register; 2. Age ≥18 years; 3. Had a filled prescription for apixaban or warfarin 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:
  Atrial fibrillation patients
• Estimated number of subjects:
  3000

Study design details

• Main study objective:
  To compare the occurrence of major bleedings in patients with atrial fibrillation (AF) treated with the combination of apixaban and dronedarone versus the combination of warfarin and dronedarone.
• Outcomes:
  The main bleeding endpoint is “major bleeding” defined as: - Any intracranial bleeding, or - Hospitalization with a bleeding diagnosis- Fatal bleed defined by a diagnosis in the Cause of Death register (underlying cause of death or first contributory cause of death), or a hospital discharge code of "4" indicating death during hospital stay in conjunction with a bleeding diagnosis. Secondary bleeding endpoints are:- Any hospitalization with a diagnosis of: - Intracranial bleed - Gastrointestinal bleed - Urogenital bleed - Other bleed - Contacts without overnight stay a bleeding diagnosis in principal or first secondary position.Death by any reason in the Cause of Death register.
• Data analysis plan:
  Detailed methodology for summary and statistical analyses of data collected in this study will be documented in a Statistical Analysis Plan (SAP), which will be dated, filed and maintained by Pfizer. For descriptive analyses describing the two cohorts at baseline, Chi2 and t-tests will be used. For time dependent analyses, made in analogy with the intention to treat principle, censoring will be made at the event, death and end of observation period. For time dependent analyses made in analogy with the on treatment principle, additional censoring will be done when a patient no longer is on combination treatment. For the assessment of bleeding events during follow up, uni and multivariable Cox regression will be used. Introduction of covariates will be done stepwise. Propensity score matching will be used. All tests will be two-sided. Confidence intervals are 95% and p-values <0.05 will be considered as significant.