Coronary heart disease outcomes among chronic opioid and cyclooxygenase-2 users compared with a general population cohort

Pharmacoepidemiol Drug Saf. 2011 Jul;20(7):754-62. doi: 10.1002/pds.2131. Epub 2011 May 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / adverse effects*
  • Cohort Studies
  • Coronary Disease / chemically induced
  • Coronary Disease / epidemiology
  • Coronary Disease / etiology*
  • Cyclooxygenase 2 Inhibitors / administration & dosage
  • Cyclooxygenase 2 Inhibitors / adverse effects*
  • Databases, Factual / statistics & numerical data
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Myocardial Infarction / chemically induced
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / etiology*
  • Myocardial Revascularization
  • Retrospective Studies
  • Risk Factors
  • Young Adult


  • Analgesics, Opioid
  • Cyclooxygenase 2 Inhibitors