Real-life anticoagulants benefit-risk in atrial fibrillation (AF) in France: VKA benefit-risk assessment before DOAC use for AF (ENGEL 1 VKA)

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

  Disease epidemiology

  Drug utilisation

  Effectiveness study (incl. comparative)
• 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:
  (B01AA) Vitamin K antagonists

  Vitamin K antagonists
• Medical condition to be studied:
  Atrial fibrillation

Population studied

• Short description of the study population:
  The study participants were new users of vitamin K antagonists for the indication of atrial fibrillation identified from national healthcare claims and hospitalisations database between 1 January 2007 and 31 December 2011 with a follow-up until 31 December 2012, and 2 years history.
• 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:
  5000

Study design details

• Main study objective:
  The main objective is to estimate the 3-month, 1-year, and 3-year risk of major bleeding, arterial thrombotic events (stroke, systemic embolism), MI and death during VKA exposure for new VKA users in AF during drug exposure.
• Outcomes:
  Major bleeding (MB) as hospitalisation with primary diagnosis of bleeding events including haemorrhagic stroke, Arterial thrombotic events (ATE) as hospitalisation with primary diagnosis of ischemic or undefined stroke or systemic arterial embolism, MI as hospitalisation with primary diagnosis of MI or acute coronary syndrome (ACS), All-cause of death, Composite criterion of MB/ATE/MI/death.
• Data analysis plan:
  Statistical analysis will be carried out according to a documented and approved Statistical Analysis Plan (SAP). The SAP describes statistical analysis as foreseen at the time of planning study. Statistical analysis will be performed after database lock using SAS® software. Blind double programming will be used for the main outcome measures. The diagnosis of AF will be considered definite if a long-term disease or hospital discharge summary with the ICD-10 code I48 were recorded before the index date, and no other indication for VKA. In the absence of definite AF, probable AF will be defined using an AF disease score, that will be a logit function of patient characteristics, including specialty of first VKA prescriber, medical acts, lab tests and drugs (ATC codes). Primary outcomes will be analysed using survival methods: The Kaplan-Meier estimate for cumulative incidence of events.