The comparative safety of analgesics in older adults with arthritis

Arch Intern Med. 2010 Dec 13;170(22):1968-76. doi: 10.1001/archinternmed.2010.391.


Background: The safety of alternative analgesics is unclear. We examined the comparative safety of nonselective NSAIDs (nsNSAIDs), selective cyclooxygenase 2 inhibitors (coxibs), and opioids.

Methods: Medicare beneficiaries from Pennsylvania and New Jersey who initiated therapy with an nsNSAID, a coxib, or an opioid from January 1, 1999, through December 31, 2005, were matched on propensity scores. We studied the risk of adverse events related to analgesics using incidence rates and adjusted hazard ratios (HRs) from Cox proportional hazards regression.

Results: The mean age of participants was 80.0 years, and almost 85% were female. After propensity score matching, the 3 analgesic cohorts were well balanced on baseline covariates. Compared with nsNSAIDs, coxibs (HR, 1.28; 95% confidence interval [CI], 1.01-1.62) and opioids (1.77; 1.39-2.24) exhibited elevated relative risk for cardiovascular events. Gastrointestinal tract bleeding risk was reduced for coxib users (HR, 0.60; 95% CI, 0.35-1.00) but was similar for opioid users. Use of coxibs and nsNSAIDs resulted in a similar risk for fracture; however, fracture risk was elevated with opioid use (HR, 4.47; 95% CI, 3.12-6.41). Use of opioids (HR, 1.68; 95% CI, 1.37-2.07) but not coxibs was associated with an increased risk for safety events requiring hospitalization compared with use of nsNSAIDs. In addition, use of opioids (HR, 1.87; 95 CI, 1.39-2.53) but not coxibs raised the risk of all-cause mortality compared with use of nsNSAIDs.

Conclusions: The comparative safety of analgesics varies depending on the safety event studied. Opioid use exhibits an increased relative risk of many safety events compared with nsNSAIDs.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Arthritis, Rheumatoid / complications*
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / epidemiology
  • Comorbidity
  • Confounding Factors, Epidemiologic
  • Cyclooxygenase 2 Inhibitors / administration & dosage
  • Cyclooxygenase 2 Inhibitors / adverse effects*
  • Disease-Free Survival
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Drug-Related Side Effects and Adverse Reactions / mortality
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Male
  • Medicare
  • New Jersey / epidemiology
  • Odds Ratio
  • Osteoarthritis / complications*
  • Pain / drug therapy*
  • Pain / etiology
  • Pennsylvania / epidemiology
  • United States


  • Analgesics, Opioid
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors