Dr. Graf also wrote that, “given the controversy already surrounding the relationship between coxibs and myocardial infarction, the excess MI risk found for users of opioids is quite thought provoking.” He noted that the statistically significant increase in all-cause mortality for patients taking opioids compared with those taking nsNSAIDs was concerning, while there was no significant difference in mortality between patients who used coxibs and those who used nsNSAIDs.
Second Study with a Twist
In their second article, “The Comparative Safety of Opioids for Nonmalignant Pain in Older Adults,” Solomon et al used a propensity-matched cohort analysis of healthcare and pharmacy insurance data collected between January 1, 1996, and December 31, 2005, for 6,275 patients taking one of five opioids: hydrocodone, codeine, oxycodone, propoxyphene, or tramadol.2
“We found that risk was not monolithic,” says Dr. Solomon. “They have different pharmacokinetics, metabolites, and pharmacodynamics. This appears to translate into different opioids having different toxicity profiles. This is very much in line with what the FDA said in November when they pulled propoxyphene. Their conclusion was that propoxyphene is associated with greater cardiovascular risk than other opioids, and we found in our study that propoxyphene was one of the riskier opioids in terms of cardiovascular toxicity.”
However, he points out, propoxyphene wasn’t the riskiest; codeine had higher relative risk of cardiovascular disease.
The authors note that the reduced risk of fracture among tramadol users compared with hydrocodone users is also a novel finding. “Opioids may cause fractures through at least two mechanisms—an increased risk of falls and an effect of opioids on bone metabolism through sex hormones,” they wrote, stating that “the increased all-cause mortality we observed for codeine and oxycodone users may relate to cardiovascular events or other unmeasured cofounders.”
In an invited commentary for this article, William C. Becker, MD, and Patrick G. O’Connor, MD, both in General Internal Medicine at Yale University School of Medicine in New Haven, Conn., noted that “prudent patient selection, thorough patient education surrounding safe medication-taking practices, and frequent patient monitoring can mitigate the incidence of overdose, addiction and diversion … . For elderly patients, in whom intentional misuse of opioid analgesics is less prevalent and medical comorbidities such as gastrointestinal or renal disease constraining the use of other analgesics is more common, experts promote opioid use as safe and effective for chronic noncancer pain.”3
They added that there are two significant implications of the study: the need to reexamine the widespread use of codeine and to implement basic safety measures to avoid fractures.
