Opioids carry increased risk for death vs NSAIDs in patients with rheumatoid arthritis
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Key takeaways:
- Opioids and NSAIDs demonstrated a similar risk for MACE in patients with rheumatoid arthritis.
- Death and venous thromboembolism were more likely among patients receiving opioids.
In patients with rheumatoid arthritis, NSAIDs and opioids demonstrate similar risks for major adverse cardiovascular events, while opioids exhibit higher rates of all-cause mortality and venous thromboembolism, according to data.
“Among the analgesics, one of the main reasons for opioid preference over non-steroidal anti-inflammatory drugs (NSAIDs) is the association of NSAIDs with cardiovascular disease (CVD), gastrointestinal and renal adverse effects,” Gulsen Ozen, MD, of the University of Nebraska Medical Center, in Omaha, Nebraska, and colleagues wrote in Annals of the Rheumatic Diseases. “Nevertheless, opioids, in addition to their known addiction and overdose risks, have been shown to increase proinflammatory cytokines, oxidative stress and cause insulin resistance, hypogonadism, physical inactivity, weight gain and increase in some CVD events compared with non-users.
“Moreover, opioids were found to delay disease modifying anti-rheumatic drug (DMARD) initiation in RA, delay and decrease absorption of antiplatelets, which could also occur for DMARDs,” they added. “Given all these risks of opioids, it is unknown if opioids are safer than NSAIDs in terms of CVD in patients with RA in whom CVD risk is already increased. Although so far only two studies have shown increased CVD event risk with opioid use compared with certain NSAIDs in mainly patients with osteoarthritis, it has not been studied in patients with RA before.”
To compare the risks for major adverse cardiovascular events (MACE) with opioids and NSAIDs in patients with RA, Ozen and colleagues analyzed data from patients in the FORWARD database who were aged 18 years and older and had no cancer diagnosis through the follow-up period. The cohort included patients who were enrolled for 1 or more year between January 1998 and December 2021. For both NSAIDs and opioids, exposure was identified as the first use of either therapy without using the other at the same time. Each participant who had used opioids was compared against two patients who received NSAIDs.
The main outcomes of interest were the occurrence of MACE — including fatal or non-fatal myocardial infarction, stroke, heart failure, venous thromboembolism or mortality due to a cardiovascular event — and all-cause mortality. The individual outcomes comprising MACE made up the secondary endpoints.
The analysis included 6,866 patients who started opioids and 13,689 patients who started NSAIDs. Among these patients, there were 212 MACE-qualifying events in the opioid group and 253 MACE-qualifying events in the NSAID group, or 20.6 events per 1,000 person-years for opioid users and 18.9 events per 1,000 person-years among those receiving NSAIDs. In addition, there were 144 deaths in the opioid group, compared with 150 deaths in the NSAID group.
According to the researchers, the rate of MACE in patients receiving opioids was “similar” to those in the NSAID group (HR = 1.02; 95% CI, 0.85-1.22), but there was a 33% increased chance of mortality in the opioid group vs. the NSAID group (HR = 1.33; 95% CI, 1.06-1.67). In addition, risk for venous thromboembolism was higher in the opioid group.
“Our results suggest that opioids are not only associated with increased all-cause mortality and [venous thromboembolism] risks but also are not safer than NSAIDs in terms of CVD in patients with RA,” Ozen and colleagues wrote. “Given the lack of benefit of opioids in long-term pain management and the multifactorial nature of the pain in RA, the use of opioids only serves as putting a band-aid on a bullet hole.”
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