The risk of ischemic cardiovascular events associated with oxycodone/naloxone use

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

  Drug utilisation
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Case-control

  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (N02AA) Natural opium alkaloids

  Natural opium alkaloids

  (N02AA01) morphine

  morphine

  (N02AA03) hydromorphone

  hydromorphone

  (N02AA05) oxycodone

  oxycodone

  (N02AB03) fentanyl

  fentanyl

  (N02AE01) buprenorphine

  buprenorphine

  (N02AG04) hydromorphone and antispasmodics

  hydromorphone and antispasmodics

  (N02AX06) tapentadol

  tapentadol
• Medical condition to be studied:
  Acute myocardial infarction

  Ischaemic stroke

Population studied

• Short description of the study population:
  Patients prescribed with extended-release (ER) high potency opioid (HPO) during January 01, 2006 to December 31, 2011.
• Age groups:
  • Infants and toddlers (28 days – 23 months)
  • Children (2 to < 12 years)
  • Adolescents (12 to < 18 years)
  • 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:
  300000

Study design details

• Main study objective:
  The main study objective is to estimate the risk of ischemic Cardiovascular (CV) events in patients receiving Targin® compared to those being prescribed extended-release (ER) oxycodone or another ER high potency opioid (HPO).
• Outcomes:
  The primary outcome is the combined endpoint of acute myocardial Infarction (MI) or acute ischemic stroke (IS). The secondary outcome will be based on a broader outcome definition examining additional ischemic CV events such as angina or transient ischemic attacks.
• Data analysis plan:
  Cohort entry is defined as the first dispensation of an extended-release high potency opioid (ER HPO). Baseline covariates will be assessed in the year preceding cohort entry. In the cohort analyses, first a drug utilization part including characteristics of HPO users as well as patterns of opioid use will be conducted. Furthermore two models will be established examining predictive factors for (i) the choice of ER HPO and (ii) for the occurrence of ischemic cardiovascular events. Following this, incidence rates overall and stratified for baseline covariates will be calculated for the outcomes in users of Targin®, ER oxycodone, ER morphine and other extended-release HPO, including patches. Additionally, a nested case-control analysis within this user cohort will be conducted to obtain confounder-adjusted estimates for the risk of myocardial infarction and ischemic stroke associated with (i) current HPO treatment or (ii) recent discontinuation or (iii) recent switch of HPO therapy.