Opioid Use, Not Just Abuse, Linked to Increased AF Risk

Deborah Brauser

November 06, 2018

CHICAGO (Revised with comments November 8, 2018 ) — Even relatively short-term use of opioids can increase the risk of developing atrial fibrillation (AF) in patients in their mid 30s, new research suggests.

A retrospective analysis of more than 850,000 veterans in the United States (mean age, 38 years) showed that 29% of the 3000 participants with AF had been prescribed an opioid, whereas only 15% of those without AF had.

In addition, after adjustment for variables such as demographics and mental health comorbidities, opioid use by itself was a significant risk factor for AF. In fact, participants with an opioid prescription were 34% more likely than those without a prescription to develop the cardiovascular (CV) condition.

Jonathan Stock

Although there have been numerous reports of opioid abuse/misuse and detrimental health outcomes, that such a poor CV outcome was shown with the use of opioids was somewhat surprising, lead author Jonathan D. Stock, MD, Yale New Haven Hospital, Connecticut, told theheart.org | Medscape Cardiology, especially in this study cohort.

"When designing this study, we thought it would be a bit of a longshot to identify a link between opioid use and atrial fibrillation in our young population, especially because it's a disease more of older people. But the association was strong enough to overcome what I had perceived to be a barrier," Stock said.

"I'd say the number one takeaway is that, although we tend to focus on opioid abuse when we think about the opioid epidemic, this research and the work of other people is starting to uncover that opioid use alone can take a human toll," he said.

The findings were released ahead of their presentation at the upcoming American Heart Association (AHA) Scientific Sessions 2018.

Assessing 857,000 Records

Stock noted that a recent study suggested a link between opioid use and CV mortality. Because of those findings, his team wanted to explore reasons for the association.

"One contributing factor for this association is speculated to be increased risk for cardiac arrhythmias, such as [AF] due to sleep-disordered breathing that can accompany opioid abuse," the investigators write.

The researchers assessed administrative and clinical data for 857,283 post-9/11 veterans 25 to 51 years of age (87.3% men, 59.0% white, 14.1% black, and 11.0% Hispanic). They also examined opioid prescription data from for 2014 and 2015.

"It's been shown that veterans use opioids in higher amounts than the general population. I suspect they have higher amounts of musculoskeletal type pain and perhaps the psychological traumas of war exacerbate that pain," Stock said.

In addition, "we used this particular cohort of veterans specifically because the average age of 38 was so low," he reported. "As we age, we accumulate more and more medical problems, which tends to muddy the waters with regard to these kinds of epidemiological studies. If we had looked at opioid use and atrial fibrillation in older people, we might have run into more confounding variables."

"We chose this younger population so that if we found an association, which we did, it would be more robust than if we had done it in a more general, older population," he explained.

Increased AF Risk

Results showed that 3033 of the participants (0.35%) had received an AF diagnosis. Opioids were prescribed more often for veterans with AF than without (29.2% vs 15.4%).

The adjusted odds ratio for AF risk in those with an opioid prescription, compared with those without a prescription, was a significant 1.34 (95% confidence interval, 1.23 - 1.45; P < .001). Opioid prescription duration was not significantly associated with the prevalence of AF.

Stock noted that more men than women in the study had AF.

"It's known that being a woman is, to some degree, protective against atrial fibrillation; it's a more common disease in men, and that particular association was also found in this study. However, even after correcting for sex, opioids were still found to be associated with atrial fibrillation in this veteran population," he said.

There were no significant race-based differences.

"This analysis of nationwide data demonstrates the independent association of opioid use to diagnosed AF," the investigators write. "Given the contribution of AF to incident cardiovascular events, these findings indicate one pathway by which opioid use may contribute to cardiovascular mortality."

Stock noted in a press release that the findings "point to the importance" of prescribing opioids as a last resort.

"Opioid use, by itself, must be taken seriously and efforts should be made not only to reduce opioid abuse and overdoses, but also to ensure that patients are being prescribed opioids only when absolutely necessary," he said.

The investigators are now planning to assess these patients to see whether other CV conditions, such as coronary disease, are more prevalent in those who use opioids, he told theheart.org | Medscape Cardiology.

Asked whether the researchers stratified opioid "users" from "abusers" in their study population, Stock said they did not distinguish between the two groups. "We just wanted everyone who was using opioids in our 1-year study period; and use alone was enough to create the association we found."

"Concerning Study"

Commenting for the American Heart Association on these findings, N.A. Mark Estes, MD, University of Pittsburgh Medical Center Heart and Vascular Institute, noted that this study "raises the distinct possibility that opioid use may be associated with an increased frequency of [AF], an uncommon rhythm disturbance in this young population."

Estes, who was not involved with the research, stressed that "important observations from the study included that" the average age of the participants was just 38 years and that the association with AF occurred with use of opioids "in normal therapeutic doses."

In addition, because there were no associations found between length of opioid use and AF development, it's possible that "even short-term use of opioids increases the risk," he said. "It's a concerning study."

Estes noted that the investigators speculated that opioid use is a contributor to disordered sleep/sleep apnea, which has itself been linked to AF, "but the precise mechanism has not been worked out."

To theheart.org | Medscape Cardiology, he noted that it was a well-done study in a large cohort that "controlled for all the usual variables." However, it was also a retrospective analysis and showed an association without proving "cause and effect," so further prospective studies are now needed. Still, he said that there's enough here to "raise a cautionary note" for clinicians.

"From a scientific point of view, it can't be said that [opioids] are a cause. Nonetheless, the important message for clinicians is to prescribe the smallest effective doses for the shortest period of time because there may be an increased risk of adverse cardiovascular effects, including atrial fibrillation," Estes concluded.

The study was funded by the Veterans Health Administration. The study authors and Estes report no relevant financial relationships.

American Heart Association (AHA) Scientific Sessions 2018: Poster abstract Sa1079. To be presented November 10, 2018

Follow Deborah Brauser on Twitter: @MedscapeDeb. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

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