Cohort Study of the Relative Incidence of Major Cardiovascular Events Among Patients Initiating Prucalopride Versus a Matched Comparator Cohort

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

• Anatomical Therapeutic Chemical (ATC) code:
  (A06AD15) macrogol

  macrogol

  (A06AX05) prucalopride

  prucalopride
• Medical condition to be studied:
  Acute myocardial infarction

  Ischaemic stroke

  Haemorrhagic stroke

  Cardiac death

Population studied

• Short description of the study population:
  The prucalopride cohort consisted of adult patients who had a dispensing (for claims data sources) or prescription (as recorded in electronic medical record data sources) for prucalopride within the study period with at least 12 months of data coverage in the data source before this first dispensing or prescription, no evidence in the data source of prior use of prucalopride, and no evidence of short use of PEG (i.e., < 5 days) within 12 months before this first prucalopride prescription/dispensing. The first prescription of prucalopride was the index prescription, which determined the index date.; The PEG cohort consisted of patients who had a dispensing or prescription for PEG of at least 5 days within the study period, who had at least 12 months of data coverage in the data source before this first dispensing or prescription, and who had no evidence of prior use of PEG for chronic constipation in the data source. The first prescription for PEG was the index prescription, prescribed or dispensed on the index date. Up to five PEG initiators were selected for each prucalopride initiator, matched by age, sex, and calendar year of first prescription of prucalopride or PEG. (The SNR also matched patients by recent hospitalization and specialty of the prescribing physician to increase comparability between PEG and prucalopride users). At the time of study initiation, PEG was the most commonly prescribed reimbursable medication for chronic constipation in Europe.
• 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:
  66900

Study design details

• Main study objective:
  To estimate the adjusted incidence rate ratio and 95% confidence interval for major adverse cardiovascular events—defined as the composite of hospitalization for acute myocardial infarction, hospitalization for stroke, and in-hospital cardiovascular death—in initiators of prucalopride versus initiators of polyethylene glycol 3350, adjusting for CV risk factors and other confounders.
• Outcomes:
  Major adverse cardiovascular events (MACE)—defined as the composite of hospitalization for acute myocardial infarction (AMI), hospitalization for stroke, and in-hospital cardiovascular death, Individual components of MACE – Hospitalization for AMI, hospitalization for stroke, in-hospital cardiovascular death
• Data analysis plan:
  For each cohort, the prevalence of baseline risk factors for MACE will be described. Incidence rates of each outcome of interest will be calculated for the prucalopride and PEG cohorts, and IRRs will be estimated. Within each data source, propensity scores will be developed by modeling use of prucalopride against CV risk factors that could be confounders. After stratifying cohort-specific incidence rates by propensity score decile and by data source, the coordinating center will conduct an overall analysis combining the results across all data sources to calculate overall summary incidence rate and IRR estimates. Overall incidence rates will be age- and sex-standardized to the distribution of person-years in the prucalopride cohort across all data sources by age category and sex. Overall IRRs will be standardized to the distribution of propensity score deciles in the prucalopride cohort across all data sources.

Documents

Study results

Study SPD555-802 Final Report Addendum 2.0_24Jan2019_abstract

Study publications

Gilsenan A, Fortuny J, Cainzos-Achirica M, Cantero AF, Flynn RWV, Garcia-Rodrig…

Fortuny J, Gilsenan A, Cainzos-Achirica M, Cantero AF, Flynn RWV, Garcia-Rodrig…

Ruigómez A, Plana E, Gilsenan A, et al. Identification and Validation of Major …