The risks of opioid use for elderly patients with nonmalignant pain vary considerably by different agents and by different durations of use, according to a report in the Dec. 13/27 issue of Archives of Internal Medicine.
Patients taking codeine for more than 180 days are at increased risk for cardiovascular events, and those taking oxycodone or codeine for only 30 days are at increased risk for mortality due to any cause, said Dr. Daniel H. Solomon and his associates in the rheumatology department and the pharmacoepidemiology division at Brigham and Women’s Hospital, Boston.
"This study’s findings do not agree with a commonly held belief that all opioids are associated with similar risk," the investigators noted.
They compared the safety profiles of different opioids for the treatment of nonmalignant pain in elderly patients because "relatively little attention has been paid" to this issue even though the use of these drugs has increased by 50%-100% in recent years. In contrast, patients and physicians are relatively well informed about the toxicities of NSAIDs used for the same indications.
Dr. Solomon and his colleagues analyzed information in two states’ Medicare databases of pharmaceutical coverage for low-income patients (mean age, 79 years) between 1995 and 2005. They were able to match 6,275 subjects who took five of the most commonly prescribed opioids for a variety of baseline factors using propensity scores.
Hydrocodone was used as the reference exposure, to which codeine, oxycodone, propoxyphene, and tramadol were compared.
The risk of cardiovascular events including MI, stroke, heart failure, revascularization, and cardiac death was similar across the five opioid groups after 30 days of use. However, by 180 days the cardiovascular risk with codeine was significantly elevated (risk ratio, 1.62), compared with the other four opioids.
This finding is surprising and requires validation in other study populations, the investigators said (Arch. Intern. Med. 2010;170:1979-86).
All-cause mortality was elevated after only 30 days of use for patients taking oxycodone (RR, 2.43) or codeine (RR, 2.05), but not for those taking other opioids.
In contrast, the risk of fracture of the hip, pelvis, wrist, or humerus was significantly reduced after 30 days of treatment for patients taking tramadol (RR, 0.21) or propoxyphene (RR, 0.54).
The risk of gastrointestinal adverse events – which included upper GI bleeding, lower GI bleeding, and bowel obstruction – did not differ across opioid groups at either 30 days or 180 days.
These risks remained consistent through a range of sensitivity analyses of the data. Importantly, the risks also were consistent regardless of whether patients were taking low, medium, high, or very high doses of the drugs. "The risks were substantial and translated into numbers needed to treat that would be considered clinically significant," Dr. Solomon and his associates wrote.
This study was supported by the Agency for Healthcare Research and Quality. Dr. Solomon reported being an unpaid member of a celecoxib trial executive committee sponsored by Pfizer and an unpaid member of the data safety monitoring board for an analgesic trial sponsored by Pfizer.