title: Coronary heart disease outcomes among chronic opioid and cyclooxygenase-2 users compared with a general population cohort.
abstract: BACKGROUND
  We estimated the incidence of myocardial infarction (MI) and coronary revascularization (CR) among users of chronic opioid therapy (COT) and compared risks across categories of morphine-equivalent doses of COT and comparator cohorts.
  
  
  METHODS
  We conducted a retrospective claims-based study using de-identified data from a commercially insured population. A cohort of 148,657 adult users of COT, a matched cohort of the general population, and three cohorts of users of chronic cyclooxygenase-2 (COX-2) inhibitor therapy totaling 122,810 were identified. Incidence rates and incidence rate ratios (IRRs) of MI and MI/CR were estimated.
  
  
  RESULTS
  Adjusted IRRs for MI ranged from 1.21 (95% confidence interval [95%CI], 1.02-1.45) among those receiving low COT doses to 1.89 (95%CI, 1.54-2.33) among those receiving high doses compared with those receiving very low doses, averaging <15 mg/day. Similar patterns were shown for MI/CR. IRRs standardized to the age-sex distribution of the general cohort and adjusted for coronary heart disease risk factors showed 2.7 times the rate of MI and 2.4 times the rate of MI/CR in the COT cohort compared with the general population. Using the same analysis, COX-2 users had 1.7-1.9 times the rate of MI and MI/CR compared with the general cohort.
  
  
  CONCLUSIONS
  Chronic analgesic use with either COT or COX-2 was associated with an increased risk of cardiovascular outcomes. These findings suggest either a selection of high-risk patients to chronic analgesic treatment, coupled with unmeasured or residual confounding, or a potential cardiovascular effect of these medications. Further research is warranted to evaluate causes for this association.
authors.affiliation: i3 Drug Safety, Ann Arbor, MI, USA. wendy.carman@i3drugsafety.com
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Carman
authors.forename: Shuhua
authors.initials: S
authors.lastname: Su
authors.forename: Suzanne F
authors.initials: SF
authors.lastname: Cook
authors.forename: John I
authors.initials: JI
authors.lastname: Wurzelmann
authors.forename: Andrew
authors.initials: A
authors.lastname: McAfee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D003327:Coronary Disease / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology*; D009204:Myocardial Revascularization; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D052246:Cyclooxygenase 2 Inhibitors