Opioids nearly double risk for venous thromboembolism vs. NSAIDs in rheumatoid arthritis
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PHILADELPHIA — Opioid use in rheumatoid arthritis demonstrates a nearly two-fold increased risk for venous thromboembolism vs. NSAIDs, according to data presented at ACR Convergence 2022.
“One of the most commonly prescribed analgesics is NSAIDs and we know that it’s been shown that it can be associated with a small increase in cardiovascular disease, gastrointestinal bleeding, some renal disease progression and other cardiovascular effects,” Gulsen Ozen, MD, a rheumatology fellow at the University of Nebraska Medical Center, said during a press conference. “These may lead to opioid prescription by some providers over NSAIDs. This has become a very big problem in the United States, and opioids are now an epidemic problem — opioid prescription can be seen in up to 60% of patients with RA.
“Unfortunately, the effects of DMARD prescription are minimal in reducing opioid use in RA patients,” she added. “Even worse, it can delay DMARD initiation, which is the most effective treatment to control the disease activity. We know that opioids have been shown to have some effects on platelet aggregation, myocardial fibrosis, oxidative stress and increased weight, and therefore because of all these risks, it can increase cardiovascular disease risk factors, too. However, it is not clear whether opioids are safe in terms of cardiovascular events compared with NSAIDs.”
To examine the risk for major cardiovascular events (MACE) with opioids compared with NSAIDs in patients with RA, Ozen and colleagues conducted a new-user active comparator cohort study within FORWARD, the National Databank for Rheumatic Diseases. According to the researchers, the cohort included adult patients with RA, and without cancer, who were enrolled in FORWARD for at least 1 year between 1998 and 2021.
In all, the analysis included 4,778 opioid and 11,218 NSAID initiating patients with RA. Baseline characteristics of patients in the matched cohort were balanced save for CVD therapies, including aspirin, antihypertensives and nonstatin antilipidemics, according to Ozen and colleagues.
The researchers matched patients who started opioids with those who received NSAIDs based on propensity scores (PS). These scores included age, sex, BMI, smoking, alcohol use, RA duration, RA disease activity, HAQ, pain VAS, joint surgeries, prior cardiovascular disease (CVD) and venous thromboembolism (VTE), hypertension, diabetes, rheumatic diseases comorbidity index, osteoporosis/fractures, thyroid, chronic liver, kidney, lung and mental health diseases, hospitalizations, SF-36 and sleep scores, DMARD use, glucocorticoids, medications influencing MACE risk and calendar year.
The primary outcomes were MACE — defined as myocardial infarction, stroke, heart failure, CVD death or VTE — and all-cause mortality. The researchers estimated risk for these outcomes using Cox proportional hazards with adjustment for PS weights and imbalanced patient characteristics after matching. Ozen and colleagues censored patients until the end of treatment plus 3 months, or end of follow-up if they remained on treatment.
According to the researchers, there were 133 instances of MACE, or 18.2 per 1,000 person-years, and 95 deaths from any cause, or 12.6 per 1,000 person years, among patients who started opioids. Among those who started NSAIDs, there were 392 instances of MACE, or 14.6 per 1,000 person-years, and 228 deaths from any cause, or 8.2 per 1,000 person-years.
In PS weighted models, the risks for MACE (HR = 1.05; 95% CI, 0.83-1.32) and all-cause mortality (HR = 1.21; 95% CI, 0.91-1.62) were similar across both the opioid and NSAID groups.
However, the risk for VTE specifically was significantly higher among those who initiated opioids than in those who started NSAIDs (HR = 2.45; 95% CI, 1.27-4.74).
“With these results, we demonstrated that opioids are not safer than NSAIDs in terms of MACE, and may even increase all-cause mortality and VTE risk,” Ozen said. “This may be a direct association either from an increase in weight or overdose potential, with some respiratory events. However, there may still be a channeling bias. Although we used propensity score matching, there are still multiple unmeasured variables, and sicker patients may be channeled to the opioid group.
“Lastly, pain is a very complex process in RA and in all other rheumatic diseases, and we know that opioids are certainly not helpful to treat all other components of that pain,” she added. “Opioids don’t have any shown benefits in long-term pain management and, obviously from our study, they are not safer than the other analgesics. We are hoping that our study guides physicians to think about other aspects of pain and reduce opioid use.”
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Ozen G. Abstract 1646. Presented at: ACR Convergence 2022; Nov. 11-14, 2021; Philadelphia (hybrid meeting).
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