From the Journals

NSAIDs a significant mediator of cardiovascular risk in osteoarthritis



A significant proportion of the increased cardiovascular disease (CVD) risk seen in people with osteoarthritis could be attributable to NSAIDs, new research has suggested.

Generic nonsteroidal anti-inflammatory drugs naproxen and ibuprofen Denise Fulton/MDedge News

Writing in Arthritis & Rheumatology, researchers reported the outcomes of a longitudinal, population-based cohort study of 7,743 individuals with osteoarthritis patients and 23,229 age- and sex-matched controls without osteoarthritis.

“The prevailing hypothesis in the OA to CVD relationship has been that OA patients frequently take NSAIDs to control their pain and inflammation and that this may lead to them developing CVD,” wrote Mohammad Atiquzzaman, a PhD student at the University of British Columbia, Vancouver, and his coauthors. However they commented that no studies had so far examined this directly in patients with osteoarthritis.

Overall, people with osteoarthritis had a significant 23% higher risk of cardiovascular disease, compared with controls, after adjustment for factors such body mass index, hypertension, diabetes, hyperlipidemia, and socioeconomic status. They also had a 42% higher risk of congestive heart failure, 17% higher risk of ischemic heart disease, and 14% higher risk of stroke.

NSAID use was five times more common among people with osteoarthritis, and NSAIDs alone were associated with a greater than fourfold higher risk of cardiovascular disease, after adjusting for osteoarthritis and other potential confounders.

When the authors performed modeling to break down the effect of osteoarthritis on CVD risk into the direct effect of osteoarthritis itself and the indirect effect mediated by NSAID use, they concluded that 41% of the total effect of osteoarthritis on cardiovascular risk was mediated by NSAIDs. The effect of NSAIDs was particularly pronounced for stroke, in which cases they estimated that the drugs contributed to 64% of the increased in risk, and in ischemic heart disease, in which they contributed to 56% of the increased risk.

Subgroup analysis suggested that conventional NSAIDs were responsible for around 29% of the total increased risk of cardiovascular disease, while selective COX-2 inhibitors, or coxibs, such as celecoxib, lumiracoxib, rofecoxib, and valdecoxib mediated around 21%. For ischemic heart disease, conventional NSAIDs explained around 45% of the increased risk, while selective coxibs explained around 32% of the risk. Similarly, with congestive heart failure and stroke, the proportion of risk mediated by NSAIDs was higher for conventional NSAIDs, compared with coxibs.

The authors noted that while a number of previous studies have found osteoarthritis is an independent risk factor for cardiovascular disease, theirs was the first study to specifically examine the role that NSAIDs play in that increased risk.

However, they noted that their information on NSAID use was gleaned from prescription claims data, which did not include information on over-the-counter NSAID use. Their analysis was also unable to include information on family history of cardiovascular disease, smoking, and physical activity, which are important cardiovascular disease risk factors. They did observe that the rates of obesity were higher among the osteoarthritis group when compared with controls (29% vs. 20%), and hypertension and COPD were also more common among individuals with osteoarthritis.

There was no outside funding for the study, and the authors had no conflicts of interest to declare.

SOURCE: Atiquzzaman M et al. Arthritis Rheumatol. 2019 Aug 6. doi: 10.1002/art.41027

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