Opioids are associated with increased risk for all-cause mortality and venous thromboembolism (VTE) and display similar risk profiles for major adverse cardiovascular events (MACE) compared with nonsteroidal anti-inflammatory drugs (NSAIDs) among patients with rheumatoid arthritis (RA), according to study results published in Annals of Rheumatic Diseases.
Investigators assessed MACE risk among patients with RA treated with opioids vs NSAIDs.
A new-user comparator cohort study was conducted using data from FORWARD, The National Databank for Rheumatic Diseases. Adult patients with RA who had no previous cancer diagnoses and participated in FORWARD between January 1998 and December 2021 were included in the analysis. Patients who initiated opioids were matched 1:2 with those who initiated NSAIDs.
Primary study outcomes included all-cause mortality and incident MACE as a composite endpoint for fatal or nonfatal myocardial infarction, stroke, heart failure, VTE or cardiovascular disease mortality.
Of the 6866 patients who initiated opioids, 212 experienced MACE at a rate of 20.6 events/1000 person-years (PYs), while 253 of the 13,689 patients who initiated NSAIDs experienced MACE at a rate of 18.9 events/1000 PYs.
At 13 months of follow-up, a total of 144 deaths occurred among patients taking opioids, corresponding to a rate of 13.5 deaths/1000 PYs. Similarly, 150 deaths occurred among patients taking NSAIDs, corresponding to a rate of 10.8 deaths/1000 PYs.
The risk for MACE was similar among patients initiating opioids or NSAIDs (hazard ratio [HR], 1.02; 95% CI, 0.85-1.22), but all-cause mortality was 33% higher among those initiating opioids vs NSAIDs (HR, 1.33; 95% CI, 1.06-1.67).
Among the specific MACE outcomes, patients initiating opioids were at greater risk for VTE compared with those initiating NSAIDs (HR, 1.41; 95% CI, 0.84-2.35).
Of the patients initiating opioids, 81% and 19% were taking weak and strong opioids, respectively. Both weak (HR, 1.51; 95% CI, 1.18-1.92) and strong (HR, 2.07; 95% CI, 1.40-3.05) opioids were associated with increased risk for all-cause mortality.
Weak (HR, 1.55; 95% CI, 1.00-4.19) and strong (HR, 2.16; 95% CI, 0.63-7.44) opioids were also associated with increased risk for VTE.
However, these increased risks were greater among patients taking strong opioids, which may indicate a dose-dependent relationship.
Among several study limitations, misclassification of drug groups was possible due to patients’ self-reporting. Additionally, the effects of opioid dose and duration on outcomes were not assessed due to inadequate data. Finally, samples for individual outcomes of MACE were likely underpowered.
The study authors concluded, “These adverse effects of opioids, along with previously reported increased risk of serious infection, fracture and delay in [disease-modifying antirheumatic drug] initiation, have important clinical implications for reducing the opioid epidemic that has not spared those with RA.”
Ozen G, Pedro S, Michaud K. Major adverse cardiovascular events and mortality with opioids versus NSAIDs initiation in patients with rheumatoid arthritis. Ann Rheum Dis. Published online July 17, 2023. doi:10.1136/ard-2023-224339