For arthritis, opioids present increased relative risk compared to NSAIDs

Opioids for arthritis pain control have an increased relative risk for many safety events compared with nonselective, nonsteroidal anti-inflammatory drugs (nsNSAIDs), a new study concluded.

Researchers examined the comparative safety of nsNSAIDs, selective cyclooxygenase 2 inhibitors (coxibs) and opioids. They studied Medicare beneficiaries from Pennsylvania and New Jersey who qualified for pharmaceutical assistance programs for low-income older adults with osteoarthritis or rheumatoid arthritis (RA). Patients had started therapy with an nsNSAID, a coxib, or an opioid in the years from 1999 to 2005. The mean age was 80 years, and almost 85% were female.

Results appeared in the Dec. 13/27 Archives of Internal Medicine alongside a second study derived from the same population and done by many of the same authors. (See the next story, "Opioids for nonmalignant pain have different adverse event profiles.")

Outcome safety events were adverse events related to analgesics: cardiovascular events (myocardial infarction, stroke, heart failure, revascularization and out-of-hospital cardiac death); gastrointestinal effects (upper and lower GI tract bleeding and bowel obstruction); acute kidney injury; hepatic toxic effects; fractures of hip, pelvis, wrist and humerus, but not spine; and trauma from a fall. Patients were matched on propensity scores.

Compared with nsNSAIDs, coxibs (hazard ratio [HR], 1.28; 95% CI, 1.01 to 1.62) and opioids (HR, 1.77; 95% CI, 1.39 to 2.24) had elevated relative risk for cardiovascular events. Gastrointestinal tract bleeding risk was reduced in patients on coxibs (HR, 0.60; 95% CI, 0.35 to 1.00) and similar for opioids. Coxibs and nsNSAIDs posed similar fracture risk. Fracture risk was elevated with opioid use (HR, 4.47; 95% CI, 3.12 to 6.41). Opioids (HR, 1.68; 95% CI, 1.37 to 2.07) but not coxibs, were associated with an increased risk for events requiring hospitalization compared with nsNSAIDs. Opioids (HR, 1.87; 95 CI, 1.39 to 2.53) but not coxibs raised the risk of all-cause mortality compared with nsNSAIDs.

The authors wrote, "Although nsNSAIDs pose certain risks, these analyses support the safety of these agents compared with other analgesics. The recent concerns raised about opioid use in nonmalignant pain syndromes appear warranted on the basis of these data."

An editorialist commented that, for a practicing internist, treating the underlying condition is as important as treating the pain. While there was likely some residual bias in which sicker patients were more likely to take opioids, "many clinicians use opioids in their patients, including the elderly, precisely for the reason that this class is perceived to be less toxic, whether out of concern for the gastrointestinal toxicity or nephrotoxicity of nsNSAIDs or the cardiovascular toxicity of coxibs, for example," the editorialist wrote. "However, the results of this study, as well as others, suggest that those assumptions may no longer hold up under more rigorous scrutiny from systematic comparative safety analyses such as this."