medwireNews: People with osteoarthritis (OA) have a significantly higher risk for developing cardiovascular disease (CVD) than those without, and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) mediates a considerable proportion of this association, researchers report.
These findings are “highly relevant because NSAIDs are some of the most commonly used drugs to manage pain in patients with OA,” said lead author Aslam Anis (University of British Columbia, Vancouver, Canada) in a press release.
“It’s important for people with OA to talk to their care providers and discuss the risks and benefits of NSAIDs,” he added.
Anis and colleagues used data from a British Columbian database to analyze CVD risk among 7,743 OA patients and 23,229 controls without OA matched on age and sex.
As reported in Arthritis & Rheumatology, crude incidence rates of CVD over an average follow-up of 9.74 years was 38.07 per 1000 person–years for people with OA, compared with 29.05 per 1000 person–years among those without, translating into a 23% elevated risk associated with OA after adjustment for factors including BMI, diabetes, hyperlipidemia, and comorbidities.
The researchers found that people with OA were significantly more likely to be using NSAIDs than non-OA controls (5.35 vs 1.07%), and people using NSAIDs were 4.14 times more likely to develop CVD than nonusers after adjustment for the presence of OA and other potentially confounding factors.
In a mediation analysis using marginal structural models, Anis et al calculated that the 23% increased risk for CVD associated with NSAID use could be separated into a direct hazard ratio of 1.13 and an indirect, NSAID-mediated hazard ratio of 1.09.
Therefore, approximately 41% of the total association between OA and CVD risk was accounted for by NSAID use, indicating that “NSAID use substantially contributes to the OA-CVD association,” they say.
In a subgroup analysis by NSAID type, the team estimated that around 29% of the OA-associated CVD risk was mediated by conventional NSAIDs including diclofenac, ibuprofen, and naproxen, while 21% was accounted for by selective COX-2 inhibitors including celecoxib, lumiracoxib, rofecoxib, and valdecoxib.
Anis and co-researchers caution that the database used in their study did not include information on factors such as family history of CVD, smoking, and physical activity, which may have influenced their results.
Nonetheless, they note that other studies support the association between NSAIDs and CVD risk, indicating that “the mediating effect of NSAIDs in OA-CVD relationship observed in the study appears to be plausible.”
And they conclude: “Future research is necessary using prospective follow up to confirm these findings.”
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