Combined bronchodilators in COPD and the risk of adverse cardio-pulmonary events: A population-based observational study (Comb Bronchodil in COPD and CardPulm AEs)

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

  Disease epidemiology
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Nested case-control analysis

Study drug and medical condition

• Name of medicine, other:
  Spririva
• Study drug International non-proprietary name (INN) or common name:
  TIOTROPIUM BROMIDE
• Anatomical Therapeutic Chemical (ATC) code:
  (R03BB) Anticholinergics

  Anticholinergics
• Medical condition to be studied:
  Chronic obstructive pulmonary disease

Population studied

• Short description of the study population:
  Chronic obstructive pulmonary disease patients who were new users of tiotropium or a a long-acting beta2-agonist (LABA) between September 25, 2003, and August 31, 2013, aged 55 years or older.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Special population of interest:
  Hepatic impaired

  Immunocompromised

  Renal impaired
• Estimated number of subjects:
  160000

Study design details

• Main study objective:
  Assess (1) the risk of acute myocardial infarction (AMI), stroke, heart failure, arrhythmia or pneumonia in combined LABA+tiotropium compared to mono treatment (2) incidence of those outcomes in LABA vs. tiotropium mono users (3) whether the risk increases for LABA or tiotropium use compared to non-use.'
• Data analysis plan:
  Time-dependent Cox proportional hazard regression models will be used to estimate hazard ratios of the outcomes for the exposures of interest in both as-treated and intention-to-treat analyses. Conditional logistic regression models will be used to perform the nested case-control analyses assessing the effects of each long-acting bronchodilator, relative to non-use.