DARWIN EU® CC - Co-prescribing of endothelin receptor antagonists (ERAs) and phosphodiesterate-5 inhibitors (PDE-5is) in pulmonary arterial hypertension (PAH)

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Disease epidemiology

  Drug utilisation

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (C02KX01) bosentan

  (C02KX02) ambrisentan

  (C02KX03) sitaxentan

  (C02KX04) macitentan

  (G04BE03) sildenafil

  (G04BE08) tadalafil
• Medical condition to be studied:
  Pulmonary arterial hypertension

Population studied

• Age groups:
  Infants and toddlers (28 days – 23 months)

  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)

  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:
  13800000

Study design details

• Main study objective:
  To describe the patient characteristics, treatment patterns of ERAs/PDE-5is, and the proportion of patients with newly diagnosed PAH who experience the events of interest (cardiovascular hospitalization, all-cause hospitalization, and death) after initiating treatment with ERAs and PDE-5is, stratified by country/database.
• Outcomes:
  Cardiovascular hospitalisation, all-cause hospitalisation, and death.
• Data analysis plan:
  The number and % of patients receiving each of a pre-specified list of PAH treatments and treatment combinations will be described. A treatment pattern analysis will be conducted to describe the sequence of prescribing of the specific ERAs/PDE-5is following diagnosis. Index date will be the date of diagnosis of PAH. Sunburst plots and Sankey diagrams will be used to describe treatment patterns and sequences over time. Large-scale patient-level characterisation will be conducted to describe age and sex at time of PAH diagnosis. The medical history will include clinical symptoms and signs, comorbidities, and important factors possibly related to PAH diagnosis. We will also report the proportion of patients with outcomes of interest. Patient-level ERAs/PDE-5is use: Patient-level features will be characterized, and the treatment duration of interest will be estimated. For all analyses a minimum cell count of 5 will be used when reporting results, with any smaller counts obscured.