Safety and Effectiveness of Rivaroxaban and Apixaban compared to warfarin in non-valvular atrial fibrillation patients in the routine clinical practice in the UK (SiERRA UK)

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

  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

• Name of medicine:
  ELIQUIS

  XARELTO
• Anatomical Therapeutic Chemical (ATC) code:
  (B01AA03) warfarin

  warfarin

  (B01AF01) rivaroxaban

  rivaroxaban

  (B01AF02) apixaban

  apixaban
• Medical condition to be studied:
  Ischaemic stroke

Population studied

• Short description of the study population:
  In the UK, nearly all residents are registered in a general medical practice that uses a system of electronic medical records. THIN is a structured, de-identified electronic medical record database in the UK. The population included in THIN is representative of the UK as a whole in terms of age, sex and geographic distribution. THIN now collects data from around 500 practices, covering about 5% of the general population of the UK population (including practices in England, Wales, Scotland, and Northern Ireland).; Inclusion criteria; -Patients aged >=18 years of age; -NVAF; -New users of Rivaroxaban, Apixaban, Warfarin; -At least one year enrollment with the general practice (GP); -One year since first health contact recorded in THIN prior to the first prescription of a study drug; Exclusion criteria; -Patients with other recent indications of OAC initiation as described in section 9.1.; -Individuals on more than one OAC on the start date.; -Users of Rivaroxaban apart from 15/20mg daily dose; -Users of Apixaban apart from 5/10mg daily dose
• 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

  Renal impaired
• Special population of interest, other:
  Ischaemic stroke
• Estimated number of subjects:
  40000

Study design details

• Main study objective:
  Primary objectives are to assess the safety and effectiveness of rivaroxaban, apixaban and warfarin in patients with non-valvular atrial fibrillation (NVAF), who appropriately and inappropriately received standard and reduced doses of each NOAC in accordance with the label.
• Outcomes:
  Risk of intracranial hemorrhage / Risk of ischemic events, Risk of intracranial hemorrhage in NVAF-patients with renal impairment or diabetes / Risk of ischemic events in NVAF-patients with renal impairment or diabetes / All-cause mortality / Drug utilisation / Drug utilisation after first intracranial hemorrhage or ischemic stroke / Patient characteristics / Patient characteristics after first intracranial hemorrhage or ischemic stroke
• Data analysis plan:
  Descriptive statistics will be used to summarize the characteristics of the study population. 95% confidence intervals will be computed for descriptive variables. We will analyze safety, effectiveness, and all-cause mortality associated to use of the study drugs in three independent nested-case control analyses. These three analyses will include all cases identified in each follow-up (respectively: intracranial hemorrhage events, ischemic events, and deaths) and an analysis-specific group of controls. These control groups will comprise a random sample of members of all three cohorts, frequency-matched by age, sex and calendar year to each set of cases. Unconditional logistic regression models will be used to obtain odds ratio estimates of oral anticoagulant use adjusted by baseline variables described above and oral anticoagulant use at index date.

Documents

Study results

20343_EU-PASS_Abstract_Redacted

Study report

SIERRA Study Report SB_27 Sep 2021