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

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  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, other:
  endothelin receptor antagonists (ERAs) and ; phosphodiesterase-5 inhibitors (PDE-5is)
• Anatomical Therapeutic Chemical (ATC) code:
  (C02KX01) bosentan

  bosentan

  (C02KX02) ambrisentan

  ambrisentan

  (C02KX03) sitaxentan

  sitaxentan

  (C02KX04) macitentan

  macitentan

  (G04BE03) sildenafil

  sildenafil

  (G04BE08) tadalafil

  tadalafil
• Medical condition to be studied:
  Pulmonary arterial hypertension

Population studied

• Short description of the study population:
  The study cohort comprised all patients with newly diagnosed PAH present in the database during the study period (2012-2022) and with at least 365 days of data availability before the day they become eligible for study inclusion. The requirement of at least 365 days of data history was also applicable to children. Therefore, children aged <1year were excluded.
• 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

• Study design:
  Retrospective cohort study in patients with newly diagnosed PAH.
• 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.
• 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.
• Summary results:
  [CONCLUSION] ; Patients with newly diagnosed pulmonary arterial hypertension (PAH) are typically older adults with a slight female preponderance, experiencing common symptoms like dyspnoea and chest pain, and often having pre; existing cardiovascular diseases. Initial PAH treatment primarily involves PDE-5 inhibitors, particularly sildenafil, with fewer patients receiving ERA monotherapy and combination therapy. The initial prescription durations for PDE-5 inhibitors and ERAs usually span one month. Patients with PAH have high hospitalization rates within one year of PAH diagnosis, and progressively increasing mortality rates.