Opioid Use for Bothersome Pain in Rheumatoid Arthritis Could Increase Thromboembolism Risk

Gulsen Ozen, MD

Data from an analysis of more than 15,000 adults with rheumatoid arthritis using opioids or nonsteroidal anti-inflammatory drugs (NSAIDs) for bothersome pain provide insight into the comparative risks of cardiovascular events and death associated with use of either agent among this patient population.

A new-user active comparator study presented at the American College of Rheumatology (ACR) Convergence 2022, results suggest opioid initiators could be at a more than 2-fold increase in risk of venous thromboembolism (VTE) than NSAID initiators

“One of the arguments for choosing opioids over NSAIDs is less impact of opioids on cardiovascular disease. However, no data supports that opioids have a safer profile than NSAIDs in addition to their other risks,” said lead investigator Gulsen Ozen, MD, a rheumatology fellow at University of Nebraska Medical Center, in a statement. “Therefore, we wanted to investigate cardiovascular risks associated with opioids compared to NSAIDs to show if they are as safe as perceived.”

With bothersome pain among the most common symptoms in people with rheumatoid arthritis, Ozen and a team of investigators sought to further explore potential associations between NSAIDs and opioids on cardiovascular and overall health. With this in mind, investigators designed their study as an analysis of data from weithin the National Data Bank for Rheumatic Diseases. Launched in 1998, the FORWARD-National Data Bank for Rheumatic Diseases is a longitudinal, observation, patient-driven database where more than 50,000 participants under the care of rheumatologists and is considered the largest patient-reported research data bank for rheumatic disease in the US, according to the FORWARD website.

For the purpose of analysis, patients included in the study were identified using propensity score-matching was based on patient age, sex, BMI, smoking, alcohol, disease duration, disease activity, HAQ, pain VAS, joint surgeries, prior cardiovascular disease and VTE, hypertension, diabetes, rheumatic diseases comorbidity index, osteoporosis/fractures, thyroid, chronic liver, kidney, lung and mental health diseases, hospitalizations, SF-36 and sleep scores, DMARDs, glucocorticoids, medications influencing major adverse cardiovascular risk, and calendar year. The primary outcomes of interest for the study were all-cause mortality and major adverse cardiovascular events (MACE), which was defined as incidence of myocardial infarction, stroke, heart failure, cardiovascular death, and VTE.

Overall, 15,996 individuals were identified for inclusion in their analyses, with 4778 classified as opioid initiators and 11,218 classified as NSAID initiators. Investigators noted baseline characteristics were well-balanced except for medications for cardiovascular disease, including aspirin, antihypertensives, and nonstatin antilipidemics.

Upon analysis, results indicated rates of MACE (18.2 vs 14.6 per 1000 person-years) and all-cause mortality (12.6 vs 8.2 per 1000 person-years) were greater among opioid initiators compared with NSAID initiators. Investigators noted that, although incidence rates of MACE and all-cause mortality were lower among NSAID initiators, the risk of MACE and all-cause mortality in propensity score-weighted models indicated rates were similar among both arms. Secondary analysis of individual components of the primary MACE outcome suggested risk of VTE was significantly greater in opioid initiators than NSAID initiators (HR, 2.45 [95% CI, 1.27-4.74]).

“Our study suggests that opioids can cause significant cardiovascular morbidity and even death in patients with rheumatoid arthritis. We hope our findings can decrease opioid prescriptions for pain in patients with inflammatory rheumatic diseases,” Ozen added. “We have to remember that pain in inflammatory rheumatic diseases is multifactorial, and we should utilize nonpharmacological methods more often in this patient population.”

This study, “Major Adverse Cardiovascular Events and Mortality with Opioids versus NSAIDs Initiation in Patients with Rheumatoid Arthritis,” was presented at ACR Convergence 22.