title: Description of cardiovascular event rates in patients initiating chronic opioid therapy for noncancer pain in observational cohort studies in the US, UK, and Germany.
abstract: BACKGROUND
  Previous observational studies in the US suggest that opioid analgesic use increases the risk of cardiovascular (CV) events. The current study provides additional background event rates for five prespecified CV outcomes of interest in patients from three countries.
  
  
  METHODS
  Three observational cohort studies were conducted in patients from the US (N = 17,604), the UK (N = 9,823), and Germany (N = 9,412). Patients were new opioid users who had undergone ≥6 months of chronic, continuous therapy. De-identified data were collated from electronic healthcare databases in the respective countries. Demographics, clinical characteristics, and opioid use were examined. Overall rates, prevalence rates in patients with established CV disease, and incidence rates in patients without established CV disease were determined for myocardial infarction (MI), stroke, transient ischemic attack, unstable angina, and congestive heart failure (CHF).
  
  
  RESULTS
  Cardiovascular disease at baseline was more prevalent in US and German patients. Back pain and depression were prevalent preexisting comorbidities. The majority of patients were using various weak opioids (based on receptor affinities), CV medications, and antidepressants. Overall rates by individual CV outcome per 1,000 patient-years by country were greatest for CHF (US 37.2, 95% CI 24.1-40.5), unstable angina (UK 8.2, 95% CI 7.0-9.6), and stroke (Germany 5.3, 95% CI 4.1-6.7). Overall rates for MI were: US, 10.7 (95% CI 9.1-12.5), UK, 6.7 (95% CI 5.6-8.0), and Germany, 2.7 (95% CI 1.9-3.7). Overall rates for each CV outcome, prevalence rates in patients with preexisting CV disease, and incidence rates in patients without established CV disease differed by country. Rates were higher in patients with preexisting CV disease.
  
  
  CONCLUSIONS
  CV risk for new opioid users with ≥6 months of therapy was increased in patients with established CV disease compared with those without established CV disease, and the risk for specific outcomes differed by country. Assessment of CV safety events of new therapies introduced to chronic opioid users should consider sample size and population heterogeneity in the design of an observational study.
authors.affiliation: AstraZeneca, Wilmington, DE, USA, robert.locasale@astrazeneca.com.
authors.forename: Robert
authors.initials: R
authors.lastname: LoCasale
authors.forename: David M
authors.initials: DM
authors.lastname: Kern
authors.forename: Pierre
authors.initials: P
authors.lastname: Chevalier
authors.forename: Siting
authors.initials: S
authors.lastname: Zhou
authors.forename: Soheil
authors.initials: S
authors.lastname: Chavoshi
authors.forename: Mark
authors.initials: M
authors.lastname: Sostek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D015331:Cohort Studies; D005260:Female; D005858:Germany; D006333:Heart Failure / Q000139:chemically induced; D006801:Humans; D002546:Ischemic Attack, Transient / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced; D010146:Pain / Q000188:drug therapy*; D015995:Prevalence; D012306:Risk; D020521:Stroke / Q000139:chemically induced / Q000453:epidemiology; D013997:Time Factors; D006113:United Kingdom; D014481:United States; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid