Use of inhaled long acting beta2 adrenoceptor agonists and the risk for Acute Myocardial Infarction (AMI). A methodological comparison across data sources and epidemiological design

Study type

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

  Disease epidemiology

  Other
• If ‘other’, further details on the scope of the study:
  Analysis of discrepancies in results between different databases

Non-interventional study

• Non-interventional study design:
  Case-control

  Cohort

  Other
• Non-interventional study design, other:
  Case-crossover, Descriptive study = description of exposure and/or outcome in the whole database during a defined period of time

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (R03AC) Selective beta-2-adrenoreceptor agonists

  Selective beta-2-adrenoreceptor agonists

  (R03BB) Anticholinergics

  Anticholinergics

  (R03CK) Adrenergics and other drugs for obstructive airway diseases

  Adrenergics and other drugs for obstructive airway diseases
• Medical condition to be studied:
  Acute myocardial infarction

Population studied

• Age groups:
  Preterm newborn infants (0 – 27 days)

  Term newborn infants (0 – 27 days)

  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:
  55700000

Study design details

• Main study objective:
  To assess the association between the use of inhaled long acting beta2adrenoceptor agonists and the risk of acute myocardial infarction with different study designs across different primary care databases and to compare the results between databases, across designs to evaluate the impact of design/database/population differences on the outcome of the studied association.
• Data analysis plan:
  DescriptivesExtensive descriptive studies will be performed to characterize and compare exposure and outcome in the databases.Cohort studyIncidence density will be calculated as the number of AMI divided by person-time. Stratified relative risk will be graphically shown with the Ramlau-Hansen method. Time-dependent Cox-regression models will be used for confounding factor adjusted analysis. Hazard ratio's will be calculated for current use of LABA compared to the control group.Nested case controlConditional logistic regression analysis will be used to estimate the risk (OR) of AMI with current use of LABA compared to the control group. OR for AMI will be estimated by comparing inhaled LABA with the control group (No-LABA) using conditional regression analysis.CCOThe Nonparametric Multiple Intervals Approach will be used. OR will be calculated with the use of conditional logistic regression, as described above