Comparative Effectiveness of Ticagrelor vs. Prasugrel in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)

  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  BRILIQUE
• Study drug International non-proprietary name (INN) or common name:
  TICAGRELOR

  PRASUGREL
• Anatomical Therapeutic Chemical (ATC) code:
  (B01AC24) ticagrelor

  ticagrelor

  (B01AC22) prasugrel

  prasugrel
• Medical condition to be studied:
  Acute coronary syndrome

Population studied

• Short description of the study population:
  The study population includes patients aged 18 or higher diagnosed with ACS undergoing PCI, administered with either ticagrelor or prasugrel. ; The index date is defined as the date of PCI, with the minimum date 2009-07-10 (the day of FDA approval of prasugrel). ; Patients with previous history of other major ischemic or hemorrhagic events, including stroke and gastrointestinal (GI) bleeding are excluded. ; Specific rules defining the index date are described below.
• 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)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)

Study design details

• Study design:
  This is a retrospective cohort study, comparing the incidence rates of effectiveness and safety outcomes. Data sources will be electronic health record (EHR) data & claims data in Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) format.
• Main study objective:
  This study is a cohort study which aims to:; I. Determine and compare the hazard of major adverse cardiovascular events (MACE); II. Determine and compare the incidence rate of net adverse clinical events (NACE) and individual outcomes, including all-cause mortality, cardiovascular mortality, ischemic events, and hemorrhagic events of ticagrelor and prasugrel in ACS patients undergoing PCI.; ;
• Setting:
  As primary analysis, intention-to-treat design will be applied to derive 1-year outcomes. ; As sensitivity analysis, intention-to-treat design will be applied to derive 1-month outcomes. ; ; Index rule defining the index date: ; • First procedure occurrence of PCI (Table 1); • With age greater or equal to 18 at the index date. ; • With continuous observation of at least 365 days before the event index date.; • At least 1 occurrence of a condition occurrence of ACS (Table 2) between 7 days before and 0 days after index start date; • At least 1 occurrence of a drug exposure to the drug of interest between 1 day before and 1 day after index start date ; Inclusion rules based on the index date:; • With no exposure to the drug of the other group or cangrelor (Table 10) between 180 days before and 0 days after index start date ; • With no exposure to warfarin or direct oral anticoagulants (DOAC) (Table 6) between 180 days before and 0 days after index start date; • With no condition occurrence of ischemic stroke (Table 3) or hemorrhagic stroke (Table 4) before and 0 days after index start date; • With no condition occurrence of GI bleeding (Table 5) before and 0 days after index start date ; ; On-treatment design will also be applied for a sensitivity analysis. In this case, the cohort exit rule described below will be applied for time at risk end.; ; Exit rules defining the cohort end date: ; • Event will persist until the end of a continuous drug exposure of interest. ; • Allowance for 14-day gaps between exposure records of the drug of interest. ; • No additional period of surveillance after the end of the era of persistent exposure; • Censored with an exposure of clopidogrel (Table 9), cangrelor or the drug of the other group ; ; ;
• Comparators:
  The target group consists of patients who were initiated with ticagrelor and who meet the criteria above. The comparator group consists of patients who were initiated with prasugrel and who meet the criteria above. ;
• Outcomes:
  The primary outcome of this study is MACE, which is defined as a composite outcome of all-cause mortality, acute myocardial infarction (AMI), stroke (ischemic and hemorrhagic).; ; For secondary outcomes, NACE is defined as a composite outcome of all-cause mortality, AMI, stroke, and GI bleeding. An ischemic event is defined as a composite outcome of AMI and ischemic stroke. A hemorrhagic event is defined as a composite outcome of hemorrhagic stroke and GI bleeding. Each inidvidual components of the composite outcomes, as well as all cause mortality and cardiovascular mortality will also be evaluated.; ; Among the secondary outcomes, cardiovascular mortality is operationally defined as death occurrence with a condition occurrence of sudden cardiac death, AMI, stroke (ischemic or hemorrhagic), or hospitalization from heart failure.
• Data analysis plan:
  Propensity score (PS) adjustment methods will be used to adjust for potential confounding biases originating from differences in baseline covariates. Absolute standardized mean differences (aSMD) before and after PS adjustment will be calculated to estimate the difference in patient characteristics in the two groups and how they are adjusted. Based on PS distribution, quantification of empirical equipoise will be achieved.; Cumulative incidence will be estimated for each group. Cox proportional hazards models will be used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). Furthermore, negative control outcomes will be used for empirical calibration and minimization of potential unmeasured confounding biases and quantify systematic error.;