Real-life anticoagulants comparative benefit-risk in nonvalvular atrial fibrillation (NVAF) in France (ENGEL 2)

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

  (B01AE07) dabigatran etexilate

  dabigatran etexilate

  (B01AF01) rivaroxaban

  rivaroxaban
• Medical condition to be studied:
  Atrial fibrillation

Population studied

• Short description of the study population:
  Participants with nonvalvular atrial fibrillation treated with direct oral anticoagulants (DOAC) (Pradaxa®, Xarelto®) and vitamin K (VKA) utilizing French nationwide claims database identified from 2013 to 31 December 2016.
• 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:
  Patients with nonvalvular atrial fibrillation
• Estimated number of subjects:
  150000

Study design details

• Main study objective:
  The main objective is to compare the one-year risk of major bleeding, risk of stroke and systemic embolism (SSE), risk of myocardial infarction (MI) and risk of death for each DOAC (Pradaxa®, Xarelto®) versus VKA in NVAF during drug exposure.
• Outcomes:
  Clinically relevant bleeding (CRB) as a hospitalisation with primary diagnosis of haemorrhagic stroke, or other critical organ or site bleeding, or other bleedings, SSE as a hospitalisation of ischemic/undefined stroke or systemic arterial embolism, Acute coronary syndrome (ACS) as a hospitalisation of MI or unstable angina, All-cause of death, Composite criterion of CRB/SSE/ACS/death. To compare the long-term risk (2-year and 3-year) of outcomes for each DOAC (Pradaxa®, Xarelto®) versus VKA and for Pradaxa® versus Xarelto® according to the initial dose (standard or reduced dose), drugs use (exposure duration, number of dispensations, medication possession ratio, withdrawal and switch), Healthcare resources use and their related costs on the 1-year of follow-up.
• 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.Primary outcomes will be analysed using survival methods: Kaplan Meier estimate and cumulative incidence function estimate for cumulative incidence of clinical outcomes, Cox proportional hazard risk model and Fine and Gray model to compare incidence of each outcome between treatment groups, for hdPS matched patients, and all patients with hdPS adjustment.The analysis of healthcare costs during the drug exposure will be performed as an “intent-to-treat” analysis on the 1-year follow-up period. Costs will be estimated according to treatment group from national health insurance and collective perspectives.