NSAIDs Account for Large Part of Osteoarthritis-CVD Link, Study Suggests

These drugs should not be first-line therapy to relieve pain and inflammation in patients with osteoarthritis, one expert says.

NSAIDs Account for Large Part of Osteoarthritis-CVD Link, Study Suggests

Consistent with the established link between nonsteroidal anti-inflammatory drugs (NSAIDs) and increased cardiovascular risk, a new study out of Canada indicates that use of NSAIDs accounts for a large part of the relationship between osteoarthritis and CVD.

In fact, NSAID use mediates about two-thirds of that association, Aslam Anis, PhD (University of British Columbia, Vancouver, Canada), reported last week at EULAR 2018, the Annual European Congress of Rheumatology, in Amsterdam, the Netherlands.

Study co-author Mohammad Atiquzzaman, a PhD candidate at the University of British Columbia, said the study, which evaluated administrative data and did not capture over-the-counter use of NSAIDs, cannot establish causality; prospective studies would be needed for that.

He told TCTMD he would therefore not recommend any changes to how patients with osteoarthritis are managed at this point, adding, however, that “patients have to be counseled really well [so] that they understand the risk factor and they use NSAIDs with caution.”

But to Gunnar Gislason, MD, PhD (University of Copenhagen, Denmark), who was not involved in the study, it is clear that NSAIDs should not be the first choice for relieving the pain and inflammation of osteoarthritis, and that alternative approaches like physiotherapy and exercise should be tried first.

“NSAIDs should be considered later in the stages of disease when you can’t use other treatment options,” he told TCTMD.

Mediating Risk

Prior research has shown that osteoarthritis is associated with CVD, but the reason for the relationship has not been fully worked out. One possibility involves the treatments these patients receive. Many are treated with NSAIDs, which have also been associated with increased cardiovascular risk and—according to recommendations from international cardiology societies—should be avoided in high-risk patients.

To explore whether NSAID use is mediating the relationship between osteoarthritis and CVD, Anis, Atiquzzaman, and colleagues performed a population-based cohort study using administrative health data from the province of British Columbia. They identified 7,743 patients with osteoarthritis who had no prior history of CVD and who were not diagnosed with rheumatoid arthritis during the study period. Those patients were matched 3:1 by age and sex to 23,229 individuals without osteoarthritis. Overall, the mean age of the participants was 65, and 56% were women.

The investigators confirmed that osteoarthritis was associated with a greater risk of CVD after adjusting for socioeconomic status, body mass index, hypertension, diabetes, hyperlipidemia, chronic obstructive pulmonary disease, and Romano comorbidity score (adjusted HR 1.23; 95% CI 1.17-1.28). Patients with osteoarthritis also had elevated risks of ischemic heart disease (adjusted HR 1.17; 95% CI 1.10-1.26), congestive heart failure (adjusted HR 1.42; 95% CI 1.33-1.51), and stroke (adjusted HR 1.14; 95% CI 1.07-1.22).

The researchers then performed a mediation analysis using a marginal structural model, an advanced statistical tool that isolates the influence of an intermediate variable, which was NSAID use in this case.

That analysis revealed that NSAID use explained 67.51% of the relationship between osteoarthritis and CVD. That figure was lower for congestive heart failure (44.77%) and higher for stroke (93.28%) and ischemic heart disease (94.53%).

Consider Other Options

Gislason said he wasn’t surprised by the magnitude of the apparent mediating effects because it’s consistent with what is known about the risks of NSAIDs.

Doctors need to explain these issues to patients with osteoarthritis, who may have additional risk factors for CVD, and convince them to try other options before starting an NSAID, Gislason argued. “If you choose the easy way out with NSAID use, then you have the downside, which is it could contribute to increased risk of cardiovascular disease,” he said. He added that doctors should also explain to patients that over-the-counter NSAID options are not safer simply because they can be purchased without a prescription.

“As physicians, as healthcare personnel, we need to be careful to consider what other choices of treatment [are available] for the individual patient and how we are going to alleviate or treat their symptoms so they can also have a good life, an active life,” Gislason concluded. “I think that’s the main message: don’t use NSAIDS as the first choice of treatment.”

  • Anis A. The role of NSAIDS in the association between osteoarthritis and cardiovascular diseases: a population-based cohort study. Presented at: EULAR 2018. June 14, 2018. Amsterdam, the Netherlands.

  • Anis and Atiquzzaman report no relevant conflicts of interest.

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