Studies have found that the risk of venous thromboembolism doubles in patients with rheumatoid arthritis

A new study presented this week at the 2022 ACR meeting at the American College of Rheumatology Annual Meeting found that adult RA patients who started taking opioids had twice the risk of developing venous thromboembolism (VTE) than those who started taking nonsteroidal anti-inflammatory drugs (NSAIDs) (abstract #1646).

Venous thromboembolism is a serious, but preventable condition that occurs
when a blood clot forms in a vein.

Pain management is a top priority
for most people with rheumatoid arthritis (RA).
Even when the disease is well controlled, about 60% of patients will continue to experience pain, and there are few safe drug strategies, including NSAIDs and opioids, to help control pain
.
One concern about NSAIDs is the increased risk of major cardiovascular events, which has increased
in patients with rheumatoid arthritis.
While many of the potential harms of opioids—addiction, overdose, and death—are well known, the risk of major adverse cardiovascular events is unclear
.
This new user-active comparison cohort study was designed to assess cardiovascular risk
in RA patients taking opioids and NSAIDs.

"One reason to choose opioids over NSAIDs is that opioids have less
impact on cardiovascular disease.
However, beyond their other risks, there is no data to support that opioids are safer than NSAIDs," explains
Gulsen Ozen, MD, a rheumatology researcher at the University of Nebraska Medical Center and lead author of the study.
"So we wanted to investigate the cardiovascular risks associated with opioids and compare them to NSAIDs to show if they are as safe
as thought.
"

The study cohort included adults with rheumatoid arthritis who participated in the FORWARD (National Rheumatology Database)
for one or more years between 1998 and 2021.
FORWARD collects patient-reported data
on socioeconomics, disease activity, treatment outcomes, disability, hospitalization, and other critical information about rheumatism.

In the study, 4778 opioid initiators were matched with 11,218 NSAIDs initiators by propensity scores, a statistical matching technique that attempts to estimate the effects of
treatment, policy, or other interventions by predicting covariates who receive treatment.
The baseline characteristics of the matched cohort were balanced, except for cardiovascular disease drugs, including aspirin, antihypertensive, and statin cholesterol-lowering drugs
.

Major adverse cardiovascular outcomes were followed including myocardial infarction, stroke, heart failure, venous thromboembolism and death, and all-cause mortality
.

Although NSAIDs had lower major cardiovascular events and all-cause mortality than opioid initiators (392 vs.
228 versus 133 and 95, respectively), the risk was similar
in the propensity score-weighted model.
The only exception was the twofold
increased risk of venous thromboembolism in the opioid group.

"We expect opioids to carry a similar risk of cardiovascular disease and somewhat increase the risk
of all-cause mortality compared to NSAIDs.
" However, we did not anticipate an increased risk of venous thromboembolism," says
Dr.
Ozen.
"While our opioid and NSAIDs groups have been well balanced in recent hospitalizations, there may be differences
in the causes of hospitalization that require opioid and NSAID-initiation.
"

Dr.
Ozen explained that while they don't have data on why patients are hospitalized, public data suggests that hip replacement patients who take opioids for a long time have more venous thromboembolic events
than those who don't.

Dr.
Ozen noted that opioid prescriptions in the rheumatology community decreased before the COVID-19 pandemic, but have increased since then and remain a problem
for many rheumatologists.

"Treating pain in people with rheumatoid arthritis is challenging because it is not always dependent on disease activity
," says Dr.
Ozen.
"While we do not have direct evidence from patients with rheumatoid arthritis, we know from people with osteoarthritis that long-term opioid use increases pain without improving function
.
Our research shows that opioids can cause severe cardiovascular disease and even death
in people with rheumatoid arthritis.
We hope that our findings can reduce the number of times
opioids are used for pain in people with inflammatory rheumatic diseases.
We must remember that pain in inflammatory rheumatic diseases is multifactorial, and we should use more non-pharmacological methods
in this category of patients.
”

Please note: This research was funded by the Rheumatology Research Foundation Residency Mentor Award
.