A RETROSPECTIVE, REAL-LIFE EVALUATION OF THE CARDIOVASCULAR DISEASE RISK ASSOCIATED WITH EXPOSURE TO PHARMACOLOGICAL SMOKING CESSATION INTERVENTIONS IN A REPRESENTATIVE UK PRIMARY CARE PATIENT POPULATION

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
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  NICOTINE

  BUPROPION

  VARENICLINE
• Medical condition to be studied:
  Cardiovascular disorder

Population studied

• Short description of the study population:
  Exposure group: Smokers with no past history of cardiovascular disease (CVD) and no recorded smoking cessation attempts using pharmacological aids in the prior year, whose first recorded smoking cessation intervention was a cessation attempt assisted by either NRT (using any of, or a combination of products) or another pharmacological smoking cessation intervention (e.g. bupropion, varenicline) at the index date. Patients must meet the following criteria:; • Aged: 18–75 years; • Have at least one year of up-to-standard (UTS) baseline data as defined by GPRD (prior to the IPD) and at least 4 weeks’ of UTS outcome data (following the IPD) or UTS data up to the time of death if death occurred within the outcome period; ; Non-exposure group: smokers with no past history of CVD and no recorded smoking cessation attempts using pharmacological aids in the prior year, whose first recorded smoking cessation intervention involved receipt of smoking cessation advice that resulted in a quit attempt unaided by pharmacological therapies at the IPD and during the outcome periods. Patients must meet the following criteria:; tients must also meet the following inclusion criteria:; • Aged: 18–75 years.; • Current smoker throughout the prior year (any quantity of cigarettes); • Received smoking cessation advice at IPD; • Have at least one year of UTS baseline data as defined by GPRD (prior to the IPD) and at least 4 weeks’ of UTS outcome data (following the IPD), or UTS data up to the time of death if death occurred within the follow-up period(s)
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
• Estimated number of subjects:
  61050

Study design details

• Main study objective:
  To compare the CVD event rate in smokers undertaking unaided smoking cessation attempts (controls) with the event rate in those attempting cessation supported by nicotine replacement therapy (NRT) (any of: nasal spray, transdermal patches, inhaler or gum and tablets) or other pharmacological smoking cessation aids (buproion or varenecline) in a representative primary care population
• Outcomes:
  The incident of the following CV events over a 4-week outcome period: CHD diagnosis and No of days from IPD, CHD-related death and No Of days from IPD, CerebroVD diagnosis and No Of Days from IPD, CerebroVD death and No of Days from IPD, Recorded GP consultations or hospital attendances for CHD or CebebroVD, including admission, A&E attendance, out-of-hours or Out-Patient Department attendance. The incident of the following CV events over a 52-week outcome period: CHD diagnosis and No of days from IPD, CHD-related death and No Of days from IPD, CerebroVD diagnosis and No Of Days from IPD, CerebroVD death and No of Days from IPD, Recorded GP consultations or hospital attendances for CHD or CebebroVD, including admission, A&E attendance, out-of-hours or Out-Patient Department attendance.
• Data analysis plan:
  All times until diagnosis (CHD or CerebroVD) and survival times (until death due to CHD or CerebroVD) will be analysed using Cox’s Proportional Hazards Models, adjusting for baseline confounders. Censored times will be 4/52 weeks (primary/secondary outcomes). Total number of GP consultations and hospital attendances for CHD or CerebroDisease during the outcome periods will be compared between treatment groups using a Poisson regression model (conditional Poisson regression model for matched analyses) to obtain estimates of consultation / hospitalisation rates relative to the control group. The model will be adjusted for over-dispersion using robust standard errors and adjustments will be made for potential baseline confounders. For all models, variables that are strongly predictive of the outcome or that are significantly different (or show trend to significance, ie. p<0.01) between the treatment groups over baseline will be treated as potential confounders.