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

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

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i3 Drug Safety, Ann Arbor, MI, USA.



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.


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.


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.


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.

[Indexed for MEDLINE]

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