Opium Use Linked to Increased Death From Cancer, CVD

Findings May Have Implications for Chronic Pain Patients

Caroline Cassels

April 17, 2012

April 17, 2012 — Opium use, which is rare in the developed world, has been linked to an increased risk for death, predominantly from cancer and cardiovascular disease, new research shows.

However, study investigators and one outside expert question whether the study findings may have implications for millions of people in the developed world who are prescribed opioids for the treatment of chronic, non-cancer pain.

Investigators found that long-term opium use, even in relatively low doses, was associated with an almost 2-fold increased risk for all-cause mortality, particularly from cancer and cardiovascular disease.

The first study to measure mortality risk in opium users vs nonusers included 50,045 participants in Iran, where opium consumption is "exceptionally common."

"[In] this large scale prospective study we found strong increased risks of death from multiple causes in opium users compared with non-users, even among those who used low doses of opium.

"These results are consistent with results of previous case-control studies in humans and animal studies suggesting deleterious health consequences of exogenous opioids such as morphine," the authors, led by Farin Kamangar, MD, PhD, MHS, MPH, professor and chairman, Department of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore, Maryland, write.

In a linked editorial, Irfan Dhalla, MD, from St. Michael's Hospital in Toronto, reinforces the study authors' point about exogenous opioids.

"In high income countries doctors rarely, if ever, encounter someone who uses opium. However, millions of patients with chronic non-cancer pain are prescribed opioids, such as morphine, codeine, oxycodone, and hydromorphone. Are these patients, like opium users, at increased risk of death? And if so, is this solely because of an increased risk of overdose, or are patients who are prescribed opioids also at increased risk of dying from cancer, cardiovascular disease, and infection?" Dr. Dhalla writes.

The study and editorial are published online April 17 in the BMJ.

Large, Prospective Study

It is estimated that worldwide, the number of persons who use opium for medicinal or recreational purposes is 20 million. According to the investigators, a small number of retrospective case-control studies or case series have linked opium use to various diseases, including esophageal cancer, bladder cancer, and coronary heart disease, among others.

However, the study investigators note, "there is little information from well designed prospective epidemiological studies on the effect of the use of opium on overall or cause specific mortality, partly because of the relatively low opium use in most established cohort studies and the difficulty of obtaining validated data."

To investigate the potential link between opium use and subsequent mortality risk, the international team of researchers examined opium use among 50,045 men and women aged 40 to 75 years living in Golestan Province in northern Iran for an average of 5 years.

Participants were enrolled in the large, prospective study between January 2004 and June 2008 and were followed until May 2011. The follow-up rate was more than 99%.

The study's primary outcomes were all-cause mortality. The most prevalent categories for causes of death included circulatory, cancer, respiratory, digestive, infectious, or external; the external category included death due to motor vehicle crashes or other unintentional injury as well as suicide.

Investigators collected data on typical amounts of opiates used, duration of use. and which of the 4 major types of opiates that were locally available were used. These included teriak and shireh, which can be smoked or ingested; sukhteh, which can only be ingested; and heroin, which can be snorted, smoked, or injected.

Causal Association

A total of 8487 (17%) participants reported opium use, with a mean duration of 12.7 years. During the follow-up period, 2145 deaths were reported. The adjusted hazard ratio (HR) for all-cause mortality associated with ever use of opium was 1.86 (95% confidence interval [CI], 1.68 - 2.06).

In addition, opium consumption was significantly associated with an increased risk for death from cancer (HR, 1.81; 95% CI, 1.56 - 2.09) and cancer (HR, 1.61; 95% CI, 1.28 - 2.03).

The researchers report that the strongest associations were seen in deaths due to asthma, tuberculosis, and chronic obstructive pulmonary disease, with hazard ratios of 11.0, 6.22, and 5.44, respectively.

The vast majority of opium users used teriak only (n = 7308). This was followed by shireh only (721) or a combination of the two. An increased mortality risk was associated with each opium subtype. However, heroin was associated with the greatest risk.

Both smoking and ingesting opium were associated with an increased mortality risk, with adjusted HRs of 2.08 and 1.68, respectively. Smoking and ingesting opium had an adjusted mortality risk of 2.34.

"Based on the overall adjusted hazard ratio for opium use of 1.86 (1.68 to 2.06), and assuming this represents a causal association, we calculate the fraction of deaths attributable to opium in this population as 14.9% (12.3% to 17.5%)," the authors write.

Caution the Best Prescription

The authors highlight the need for further epidemiological studies examining the link between opium and mortality as well as a need to investigate the impact of the long-term use of opioid analgesics in pain patients.

Dr. Dhalla notes that in the United States, one study showed that all-cause mortality was twice as high in older patients with osteoarthritis who were prescribed opioids than in their counterparts who received nonsteroidal anti-inflammatory drugs.

He cites another study that showed that deaths in young and middle-aged adults who were prescribed opioids were more common than in their counterparts who did not take these medications, and that overdose was not the primary driver of this difference.

"In an era when doctors are increasingly becoming aware of the harms caused by prescription opioids, the findings of...[this] study should remind us not only that opium is harmful, but also that opioids have substantial risks that are incompletely understood. For the management of chronic non-cancer pain, a better prescription may be caution," Dr. Dhalla writes.

The study investigators and Dr. Dhalla have disclosed no relevant financial relationships.

BMJ. Published online April 17, 2012. Abstract, Editorial

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