Codeine Linked to Increased Cardiovascular Events

Codeine use incurs an increased risk for cardiovascular (CV) events after six months, as well as an increased risk for all-cause mortality after only 30 days, according to a new study.

Researchers at Brigham and Women's Hospital (Boston, MA, USA) devised a propensity-matched cohort study of 6,275 subjects to compare the safety of the five opioid groups commonly used for nonmalignant pain: codeine phosphate, hydrocodone bitartrate, oxycodone hydrochloride, propoxyphene hydrochloride, and tramadol hydrochloride. The study participants were new initiators of opioid therapy for nonmalignant pain; none had a cancer diagnosis, and none was under hospice or nursing home care. The main outcome measures were incidence rates and rate ratios (RRs) for CV events, fractures, gastrointestinal events, and several composite end points.

The results showed that the risk of CV events was similar across opioid groups 30 days after the start of opioid therapy, but it was elevated for codeine after 180 days. After 30 days of opioid exposure, the risk of fracture was significantly reduced for tramadol and propoxyphene users, when compared with hydrocodone; the risk of gastrointestinal safety events did not differ across opioid groups. All-cause mortality was elevated after 30 days for oxycodone and codeine users, compared with hydrocodone users. The study was published in the December 13, 2010, issue of Archives of Internal Medicine.

"This study's findings do not agree with a commonly held belief that all opioids are associated with similar risk,” concluded lead author Daniel Solomon, MD, MPH, and colleagues of the division of rheumatology. "The rates of safety events among older adults using opioids for nonmalignant pain vary significantly by agent.”

The opiate Codeine (3-methylmorphine) is a natural isomer of methylated morphine used for its analgesic, antitussive, and antidiarrheal properties, and is considered the prototype of the weak to midrange opioids. Codeine is currently the most widely used opiate in the world, and probably the most commonly used drug overall, according to numerous reports, including those of the World Health Organization (WHO, Geneva, Switzerland).

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