title: The comparative safety of opioids for nonmalignant pain in older adults.
abstract: BACKGROUND
  Severe nonmalignant pain affects a large proportion of adults. Optimal treatment is not clear, and opioids are an important option for analgesia. However, there is relatively little information about the comparative safety of opioids. Therefore, we sought to compare the safety of opioids commonly used for nonmalignant pain.
  
  
  METHODS
  We devised a propensity-matched cohort analysis that used health care utilization data collected from January 1, 1996, through December 31, 2005. Study participants were Medicare beneficiaries from 2 US states who were new initiators of opioid therapy for nonmalignant pain, including codeine phosphate, hydrocodone bitartrate, oxycodone hydrochloride, propoxyphene hydrochloride, and tramadol hydrochloride; none had a cancer diagnosis, and none were using hospice or nursing home care. Our main outcome measures were incidence rates and rate ratios (RRs) with 95% confidence intervals (CIs) for cardiovascular events, fractures, gastrointestinal events, and several composite end points.
  
  
  RESULTS
  We matched 6275 subjects in each of the 5 opioid groups. The groups were well matched on baseline characteristics. The risk of cardiovascular events was similar across opioid groups 30 days after the start of opioid therapy, but it was elevated for codeine (RR, 1.62; 95% CI, 1.27-2.06) after 180 days. Compared with hydrocodone, after 30 days of opioid exposure the risk of fracture was significantly reduced for tramadol (RR, 0.21; 95% CI, 0.16-0.28) and propoxyphene (0.54; 0.44-0.66) users. The risk of gastrointestinal safety events did not differ across opioid groups. All-cause mortality was elevated after 30 days for oxycodone (RR, 2.43; 95% CI, 1.47-4.00) and codeine (2.05; 1.22-3.45) users compared with hydrocodone users.
  
  
  CONCLUSIONS
  The rates of safety events among older adults using opioids for nonmalignant pain vary significantly by agent. Causal inference requires experimental designs, but these results should prompt caution and further study.
authors.affiliation: Division of Pharmacoepidemiology, Brigham and Women's Hospital, Boston, MA 02115, USA. dsolomon@partners.org
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Solomon
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Rassen
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Glynn
authors.forename: Katie
authors.initials: K
authors.lastname: Garneau
authors.forename: Raisa
authors.initials: R
authors.lastname: Levin
authors.forename: Joy
authors.initials: J
authors.lastname: Lee
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schneeweiss
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000453:epidemiology* / Q000401:mortality; D003061:Codeine / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011431:Dextropropoxyphene / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D050723:Fractures, Bone / Q000139:chemically induced / Q000453:epidemiology* / Q000401:mortality; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000453:epidemiology* / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D006853:Hydrocodone / Q000008:administration & dosage / Q000009:adverse effects; D015994:Incidence; D008297:Male; D006278:Medicare; D016017:Odds Ratio; D010098:Oxycodone / Q000008:administration & dosage / Q000009:adverse effects; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D014147:Tramadol / Q000008:administration & dosage / Q000009:adverse effects; D014481:United States
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D014147:Tramadol; D006853:Hydrocodone; D010098:Oxycodone; D011431:Dextropropoxyphene; D003061:Codeine