Net clinical benefit of vitamin K antagonists versus direct oral anticoagulants for nonvalvular atrial fibrillation

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Effectiveness study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

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

  warfarin

  (B01AA07) acenocoumarol

  acenocoumarol

  (B01AE07) dabigatran etexilate

  dabigatran etexilate

  (B01AF01) rivaroxaban

  rivaroxaban

  (B01AF02) apixaban

  apixaban

  (B01AF03) edoxaban

  edoxaban
• Medical condition to be studied:
  Atrial fibrillation

  Transient ischaemic attack

  Ischaemic stroke

  Pulmonary embolism

  Myocardial infarction
• Additional medical condition(s):
  Major bleeding

Population studied

• 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)
• Estimated number of subjects:
  500000

Study design details

• Main study objective:
  To assess the net clinical benefit (combined risk of suffering acute non-fatal atherothrombotic events, major bleeding or death) asociated with the exposure of vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC) in patients with nonvalvular atrial fibrillation (NVAF).
• Outcomes:
  Primary composite outcome: risk of suffering acute non-fatal atherothrombotic events, major bleeding or death with VKA or DOAC. Primary safety outcome: risk of suffering major bleeding. - Risk of primary outcome combined for each active principle. Risk of each individual component of the composite primary outcome. - Risk of each individual component of the composite primary outcome.
• Data analysis plan:
  1. Primary outcome incidences per 1000 person-years by sex and age group. 2. Outcome analysis through multilevel survival models. 3. Outcome analysis by subgroups: >74 years, naïve to anticoagulants, secondary prevention, chronic renal failure. 4. Sensitivity analysis of the primary composite outcome by: time of exposition to the anticoagulant, diary dosis of DOAC, level of effective anticoagulation with VKA, ischaemic and bleeding risk. 5. Analysis of the primary composite outcome for edoxaban by renal function. 6. Sensitivity analysis of major bleeding excluding traumatic major bleedings.