Bendroflumethiazide versus Indapamide for Primary Hypertension: Observational (BISON) study within CPRD

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Disease epidemiology

  Drug utilisation

  Effectiveness study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (C03AA01) bendroflumethiazide

  bendroflumethiazide

  (C03BA11) indapamide

  indapamide
• Medical condition to be studied:
  Hypertension

Population studied

• 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:
  200000

Study design details

• Main study objective:
  To compare, in an observational study using CPRD data, the effect of bendroflumethiazide versus indapamide on of risk of myocardial infarction (MI), acute coronary syndrome, stroke, acute decompensated heart failure & death from cardiovascular causes, in patients with hypertension.
• Outcomes:
  The first occurrence of any event within the composite outcome of myocardial infarction (MI), acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, death from cardiovascular causes. The individual components of the primary composite outcome described above, death from any cause, primary outcome or death from any cause.
• Data analysis plan:
  We will analyse time trends in the incidence of hypertension between 1987 and 2015 by sex, age and year of diagnosis. We will describe the antihypertensive therapies prescribed following the diagnosis of hypertension. We will assume that patients were treated with either bendroflumethiazide or indapamide if they received at least two prescriptions for that medication following the diagnosis of hypertension. We will construct two groups by matching patients on a propensity score, namely the probability of exposure to either indapamide or bendroflumethiazide, estimated from a logistic regression model. Time from the Index date to the outcome will be analysed using Cox proportional hazards model. We will conduct two types of analysis: per protocol primary analysis (considering patients only when they were exposed) and intention to treat sensitivity analysis (follow up until outcome or last follow up irrespective whether treatment was discontinued, switched or intensified).