Benefit-Risk Of arterial THrombotic prEvention with Rivaroxaban for atrial fibrillation in daily clinical practice. A French cohort within the nationwide claims and hospital database (BROTHER).

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 data collection

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (B01AA) Vitamin K antagonists

  (B01AE07) dabigatran etexilate

  (B01AF01) rivaroxaban
• Medical condition to be studied:
  Atrial fibrillation

Population studied

• Short description of the study population:
  The study focused on subjects with a specific or sensitive diagnosis of non-valvular Atrial Fibrillation (NVAF) and a first reimbursed dispensation of rivaroxaban, dabigatran, or vitamin K antagonists in 2013 or 2014, and no previous anticoagulant dispensation in the previous three years. Two NVAF cohorts was defined: a specific cohort for main analysis to minimize the risk of false positives, and a sensitive cohort for secondary analysis to minimize the risk of false negatives.
• 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:
  Non valvular atrial fibrillation patients
• Estimated number of subjects:
  150000

Study design details

• Main study objective:
  The main objective is to compare the one-year and two-year risk of the following individual outcomes: SSE, major bleeding and death between new users of anticoagulant for SPAF during drug exposure: rivaroxaban versus VKA, and rivaroxaban versus dabigatran (standard and reduced doses).
• Outcomes:
  SSE as a hospitalisation with primary diagnosis of ischemic/undefined stroke, or other systemic arterial embolism or surgical procedure for systemic arterial embolism, Major bleeding as a hospitalisation with primary diagnosis of haemorrhagic stroke or other critical organ or site bleeding, or other bleeding with blood transfusion during hospital stay, or resulting in death, All-cause of death. Composite of SSE, major bleeding and death, CRB as a hospitalisation with primary diagnosis of haemorrhagic stroke (linked or associated diagnosis also included), or other critical organ or site bleeding, or gastro-intestinal or urogenital or other bleeding, ACS as a hospitalisation with main diagnosis of myocardial infarction or unstable angina, drug use, Healthcare resources use and costs.
• 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 main outcome measures.Primary outcomes will be analysed using survival methods: Kaplan-Meier estimate or cumulative incidence function estimate for cumulative incidence of clinical outcomes, Cox proportional hazard risk model or Fine and Gray model to compare incidence for outcomes between rivaroxaban versus dabigatran, and rivaroxaban versus VKA (standard and reduced doses), 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. Costs will be estimated according to treatment group from national health insurance and collective perspectives.

Documents

Study results

BROTHER_Study_report_1-year_follow-up_V3.0_Clean_20181120

BROTHER_Study_report_2-year_follow-up_V1.0clean_20181116

Study publications

Blin P, Fauchier L, Dureau-Pournin C, Sacher F, Dallongeville J, Bernard MA, La…