Post-authorization Safety Study Evaluation of Cardiovascular Events in Users of Mirabegron and Other Treatments for Overactive Bladder

Study type

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

  Drug utilisation
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (G04BD12) mirabegron

  mirabegron

Population studied

• Short description of the study population:
  The study population consisted of patients who contributed episodes of person-time during new use of medications for the treatment of OAB. A new user of any drug of interest was a patient who received a prescription or dispensing for mirabegron or any antimuscarinic OAB drug during the study period, was at least 18 years of age at the time of the prescription or dispensing, and without a prescription or dispensing for the same specific medication in the previous 12 months. At cohort entry, this definition permitted a person to be either a naïve new user or a non-naïve new user. The predicted probability of starting treatment with mirabegron relative to antimuscarinic medications, conditional on baseline covariates, was estimated to create a propensity score (PS). The cohorts were then formed by PS-matching at a ratio of 1 episode of mirabegron use to 1 comparator episode of antimuscarinic medication use. The PS for each eligible episode was calculated using baseline data for that episode. By updating the covariates included in the PS for each episode contributed by a patient, time-dependent changes in baseline covariates were incorporated into the matching process.; The study included treatment episodes from males and females. The patient episodes in the study will be required to meet all of the following inclusion criteria as ascertained from each of the automated data sources:; 1. Have a recorded prescription or dispensing for mirabegron or comparator antimuscarinic medication (oxybutynin, tolterodine, darifenacin, solifenacin, trospium, or fesoterodine), with no dispensing or prescription for that specific medication in the prior 12 months before cohort entry (defined as the index prescription or dispensing). The index prescription will be considered the first treatment episode; once a patient enters the cohort (mirabegron or antimuscarinic medications [as a group]), a patient may switch between individual antimuscarinic medications and mirabegron.; 2. Be aged 18 ye
• 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)
• Estimated number of subjects:
  100000

Study design details

• Main study objective:
  Estimate and compare the incidence of CV endpoints within the person-time among users of mirabegron relative to antimuscarinic medication, (a) overall, (b) stratified by naïve user status, (c) restricted to patients 65+ years, (d) restricted to patients at high risk for CV events, (e) by intervals of time since initiation, and (f) by cumulative dose.
• Outcomes:
  Acute myocardial infarction, stroke, CV mortality, Major Adverse Cardiovascular Events (MACE) composite outcome, all-cause mortality.
• Data analysis plan:
  Database-specific and meta analyses will be performed. Within each database, mirabegron and antimuscarinic initiators will be 1:1 propensity score matched. Cox proportional hazards regression models will be built for each CV outcome. Models will be developed for: overall study population, stratified by naïve user status, patients 65+ years, patients at high risk for CV events, by intervals of time since initiation, and cumulative dose.

Documents

Study results

178-cl-114-clgr-disc01-en-final-02