Sequential Expansion of Comparative Effectiveness of Oral Anticoagulants: A Cohort Study

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)

  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  PRADAXA
• Study drug International non-proprietary name (INN) or common name:
  DABIGATRAN ETEXILATE

  WARFARIN
• Anatomical Therapeutic Chemical (ATC) code:
  (B01A) ANTITHROMBOTIC AGENTS

  ANTITHROMBOTIC AGENTS

  (B01AE07) dabigatran etexilate

  dabigatran etexilate

  (B01AA03) warfarin

  warfarin
• Medical condition to be studied:
  Atrial fibrillation

Population studied

• Short description of the study population:
  Patients ≥18 years with a diagnosis of non-valvular atrial fibrillation (NVAF) at risk for stroke (CHA2DS2-VASc score ≥ 1) who initiated treatment either with warfarin, dabigatran, rivaroxaban or apixaban between October 2010 and September 2015.
• 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:
  120.000

Study design details

• Study design:
  Observational cohort study
• Main study objective:
  Quantify associations between anticoagulant choice (warfarin and dabigatran) and the occurence of selected outcomes in patients with non-valvular atrial fibrillation at risk of stroke
• Setting:
  US MarketScan® Commercial Claims and Encounters database and Medicare Supplement (MarketScan) and OptumClinformatics Research Database (Optum)
• Outcomes:
  StrokeMajor bleeding, Stroke or systemic embolismSystemic embolismIschemic strokeHemorrhagic strokeStroke uncertain classificationTransient ischemic attackMyocardial infarctionVenous thromboembolismDVTPulmonary embolismMajor intracranial bleedingMajor extracranial bleedingMajor GI bleedingMajor upper GI bleedingMajor lower GI bleedingMajor urogenital bleedingMajor other bleeding
• Data analysis plan:
  After identifying initiators of warfarin or dabigatran with an existing diagnosis of non-valvular atrial fibrillation and at risk for stroke in two large US commercial claims databases we will use propensity score methods and time-to-event analyses to estimate the ratio in hazard rates for each of the outcomes of interest.
• Summary results:
  Discussion: The final analyses from this monitoring program remain consistent with what we observed in the interim reports which suggested a reduced risk of both primary outcomes (stroke and major bleeding) with dabigatran relative to warfarin. The primary outcomes were studied across a range of assumptions regarding exposure and within numerous subgroups and these sensitivity analyses were consistent with the results from the primary analyses. Although pooled results in the full cohort are robust, comparative conclusions within; some subgroups separately by database remain limited by patient numbers and relatively short follow-up. For the secondary comparisons, analyses suggested a reduced risk of stroke but a similar risk of major bleeding for the ; comparison of rivaroxaban versus warfarin. For the comparison of apixaban versus warfarin, the analyses suggested a reduced risk for both stroke and major bleeding.