Unfortunately, disease-modifying antirheumatic drugs (DMARDs) have minimal effects in reducing opioid use in RA patients and may even delay the initiation of the most effective treatment for controlling the disease activity.
Opioids have been shown to have effects on platelet aggregation, myocardial fibrosis, oxidative stress, and weight gain, which can increase cardiovascular disease risk factors. However, it is unclear whether opioids are safe in terms of cardiovascular events compared to NSAIDs.
To examine the risk of major cardiovascular events (MACE) with opioids compared to NSAIDs in patients with RA, researchers conducted a new-user active comparator cohort study within FORWARD, the National Databank for Rheumatic Diseases. The cohort included adult patients with RA, who were enrolled in FORWARD for at least one year between 1998 and 2021, and who did not have cancer.
The analysis included 4,778 opioid and 11,218 NSAID-initiating patients with RA. The researchers matched patients who started opioids with those who received NSAIDs based on propensity scores, which included various patient characteristics such as age, sex, BMI, smoking, alcohol use, RA duration, RA disease activity, and various comorbidities. The primary outcomes were MACE, defined as myocardial infarction, stroke, heart failure, cardiovascular disease death, or venous thromboembolism (VTE), and all-cause mortality.
The researchers found that opioid use in RA patients demonstrated a nearly two-fold increased risk for VTE compared to NSAIDs. 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 and all-cause mortality 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. The results suggest that opioids are not safer than NSAIDs in terms of MACE, and may even increase all-cause mortality and VTE risk.
The study had some limitations, such as the possibility of unmeasured variables, and sicker patients being channeled to the opioid group. Pain is a very complex process in RA and other rheumatic diseases, and opioids are not helpful in treating all components of that pain. Opioids do not have any demonstrated benefits in long-term pain management, and the study's authors hope that it guides physicians to think about other aspects of pain and reduce opioid use.