Safety of Opioid Treatment for Noncancer Pain among Older Adults

According to researchers, the use of opioids has increased 50% to 100% in recent years, despite conflicting recommendations from agencies such as the World Health Organization (WHO) and the US Food and Drug Administration (FDA). The WHO has suggested that too little attention was being given to treating pain, citing restrictions of prescribing opioids for nonmalignant pain, while the FDA has issued warnings about the dangers of opioids and has required manufacturers to document safety of the drugs through new Risk Evaluation and Mitigation Strategies. Noting that there is “relatively little information” available on the comparative safety of opioids, researchers at Brigham and Women’s Hospital in Boston, Massachusetts, recently conducted an observational study to compare the safety of opioid therapy for noncancer-related pain in older adults. They reported study results in Archives of Internal Medicine [2010;170(22):1979-1986]. The study cohort included Medicare beneficiaries from 2 states who qualified for pharmaceutical assistance programs for low-income older adults between January 1, 1996, and December 31, 2005. The participants were new initiators of opioid therapy for pain not related to cancer. The opioid studies included codeine phosphate, hydrocodone bitartrate, oxycodone hydrochloride, propoxyphene hydrochloride, and tramadol hydrochloride. None of the participants had a cancer diagnosis or were using nursing home or hospice care. The primary outcome measures were incidence rates and rate ratios (RRs) for 95% confidence intervals (CIs) for cardiovascular events, fractures, gastrointestinal events, as well as several composite end points. There were 6275 subjects in each of the 5 opioid groups. Baseline characteristics were similar across all 5 groups; mean age was 79 years, 80.9% were female, and 91.0% were white. The mean number of acute care hospital days was slightly higher for users of oxycodone compared with users of other opioids (4.4 vs 3.7, 3.6, 4.1, and 3.5). Fewer oxycodone users were women (74.3% vs 80.4%, 80.6%, 84.0%, and 85.2% in the other 4 groups). Using hydrocodone as the reference exposure, RRs were calculated across 6 safety events (cardiovascular events, fracture, gastrointestinal, hospitalized safety event, hospitalized death, all-cause mortality) at 30 and 180 days of exposure to opioids. Following 30 days of opioid use, the incidence rates of all 6 safety events were high. At 30 days of opioid use, the risk for cardiovascular events was similar across the 6 groups; at 180 days, the risk was elevated for codeine (RR, 1.62; 95% CI, 1.27-2.06). In the tramadol group, the risk of fracture was significantly reduced during the initial 30 days of use (RR, 0.21; 95% CI, 0.16-0.28). The risk of fracture was also reduced in the group using propoxyphene (RR, 0.54; 95% CI, 0.44-0.66). In all 6 groups, there was no difference in the risk of gastrointestinal safety events at either 30 or 180 days. After 30 days, the risk of all-cause mortality was increased for oxycodone users (RR, 2.43; 95% CI, 1.47-4.00) and codeine users (RR, 2.05; 95% CI, 1.22-3.45). Limitations cited by the researchers included analyzing typical practice data from a nonrandomized setting, allowing the possibility of the results being biased by residual confounding. In addition, the study database was limited because it contained healthcare and pharmacy utilization data, but did not include data on cause of death from death certificates, pain levels, functional status, aspirin or tobacco use, or over-the-counter medication use, which may have led to misclassification of exposure and outcomes. In conclusion, the researchers summarized the results, stating that the “rates of safety events among older adults using opioids for nonmalignant pain vary significantly by agent.” They added that, “Causal inference requires experimental designs, but these results should prompt caution and further study.”