Elderly patients with arthritis who regularly take opioids for pain experience more undesirable and sometimes dangerous side effects than those on other painkillers, such as Coxibs and NSAIDs (non-steroidal anti-inflammatory drugs), researchers from Brigham and Women’s Hospital, Boston, reveal in Archives of Internal Medicine.

Opioids are a class of drugs commonly prescribed for their painkilling (analgesic) properties. They include substances such as codeine, oxycodone, methadone, or morphine. They may be more easily recognized by the brand names, such as OxyContin, Kadian, Demerol, Percocet, Avinza, Percodan, Darvon, , Vicodin, and Lomotil.

The authors wrote:

    “In the United States, one in five adults received a prescription for an analgesic in 2006, accounting for 230 million prescription purchases; however, the comparative safety of these drugs is unclear. Although the cardiovascular safety of nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) and selective cyclooxygenase-2 inhibitors (coxibs) has been called into question, there is little comparable information about the third major analgesic group, opioids.”

Daniel H. Solomon, M.D., M.P.H., at Brigham and Women’s Hospital, Boston and team set out to compare the safety of opioids, Coxibs and NSAIDs among 12,840 Medicare beneficiaries. They had all been given one or more of these painkillers between 1999 and 2005. By gathering data from an extensive claims database, the researchers worked out how many of them developed heart attacks, stroke, heart failure, gastrointestinal tract bleeding, bowel obstruction, liver toxicity, acute kidney injuries, and bone fractures.

They found that patients on opioids had a higher risk of experiencing adverse events compared to those on NSAIDs or Coxibs. Those on NSAIDs had the lowest risk.

The authors reported 101 fractures per 1,000 patients among those on opioids annually, compared to just 19 for those on Coxibs.

Cardiac risk was lower for those on NSAIDs compared to coxib or opioids users.

Opioid usage was linked to a higher risk of death or hospitalization than NSAID usage. Coxib users had the same risk as NSAID users.

21 per 1,000 NSAID users annually experience gastrointestinal tract bleeding, compared to 12 per 1,000 among coxib users.

The authors wrote:

    “Analgesics are used daily by millions of people; however, current data do not allow patients or physicians to determine which type of agent is safest. We compared nsNSAIDs, coxibs and opioids across a wide range of specific safety events and several composite safety events. 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 non-malignant pain syndromes appear warranted on the basis of these data.”

In another article in the same journal (same issue), Dr. Solomon and team gathered data just on Medicare beneficiaries who took opioids for non-malignant pain for the period 1996-2005.

6,275 patients on five types of opioids – tramadol, propoxyphene, codeine, hydrocodone, and oxycodone – were compared for adverse events rates after 30 and 180 days.

Gastrointestinal adverse events risks were similar across all groups throughout the study period, the authors report. Cardiovascular events risk was similar across all groups after 30 days, but at 180 days those on codeine had significantly higher cardiovascular events risk.

When using hydrocodone as a reference point, tramadol users had a 79% lower risk of fracture and those on propoxyphene had a 46% lower risk.

The risk of death was 2.4 times higher among oxycodone users when compared to hydrocodone, and two times higher among codeine users.

The authors wrote:

    “This study’s findings do not agree with a commonly held belief that all opioids are associated with similar risk. The risks were not explained by the dosage being prescribed and did not vary across a range of sensitivity analyses. The risks were substantial and translated into numbers needed to treat that would be considered clinically significant. Our findings regarding cardiovascular risk were surprising and require validation in other data sets.”

The authors stress that an experimental design is required to prove a cause-and-effect relationship between opioids and adverse events, rather than an observational one..“but these results should prompt caution and further study.”

During a follow-up of a clinical trial, researchers found that approximately 189 days after patients had stopped taking Rofecoxib, their risk of cardiovascular events increased significantly. This was reported in a separate research letter published in the same journal.

“The Comparative Safety of Opioids for Nonmalignant Pain in Older Adults”
Daniel H. Solomon, MD, MPH; Jeremy A. Rassen, ScD; Robert J. Glynn, PhD, ScD; Katie Garneau, BA; Raisa Levin, MSc; Joy Lee, BA; Sebastian Schneeweiss, MD, ScD
Arch Intern Med. 2010;170(22):1979-1986. doi:10.1001/archinternmed.2010.450

Written by Christian Nordqvist