Celecoxib Linked with Dystrophic Valve Calcification, Aortic Stenosis

Celecoxib, a popular arthritis drug, showed an association with dystrophic valve calcification, according to a new analysis published in the Journal of the American College of Cardiology: Basic to Translational Science.

The research team began their work studying whether celecoxib (Celebrex, Pfizer) as a potential pharmaceutical alternative to surgical replacement of the aortic valve, as no effective pharmaceutical treatment currently exists. Their initial research identified CDH11 (a transmembrane cell adhesion protein) as a potential therapeutic target that had increased expression in calcified human aortic valves. Celecoxib was one of the drugs that was shown in previous analyses to bind CDH11 with high affinity.

Patient Records Analyzed

The study was an analysis of more than 8,600 patient records at Vanderbilt University Medical Center. The researchers, following results obtained from in vitro experiments on dystrophic calcification and the potential clinical significance of celecoxib use in porcine models, then looked at anonymous patient records and queried for possible associations between aortic stenosis and celecoxib, naproxen, or ibuprofen use. Their unadjusted analyses suggested that celecoxib was associated with an increased risk for developing aortic stenosis (OR=1.36; 95% CI, 1.11 to 1.67, P=0.003), an association that persisted after adjustment for age, sex body mass index, and known aortic stenosis factors. No associations were observed with naproxen or ibuprofen use.

The researchers noted that this suggested a unique relationship between celecoxib and selective COX2 inhibition associated with aortic stenosis.

“Considering the indications for celecoxib, these results suggest that physicians must carefully balance the risks of COX1 inhibition in the gut with those of COX2-specific inhibition in the aortic valve when choosing a pain control regimen, and use celecoxib with caution in elderly patients with risk factors for aortic stenosis,” the researchers wrote in the study. “Additional clinical studies are needed to confirm the link between celecoxib use and the development or progression of aortic stenosis, as this could influence prescribing patterns for medications that relieve inflammatory pain.”

Earlier Study Showed Safety

The study was noteworthy because an earlier study published in the New England Journal of Medicine in 2016 suggested that celecoxib was noninferior to naproxen and ibuprofen regarding risk for cardiac death, nonfatal myocardial infarction, or stroke. The study did not, however, look at valve disease.

“In this study, we’re adding a long-term perspective on celecoxib use,” said Megan Bowler, PhD, a medical student in biomedical engineering at Vanderbilt and coauthor on the study, said in a press release. “Calcification in the aortic valve can take many years. So if you’re at a higher risk for it, you might want to consider taking a different painkiller or rheumatoid arthritis treatment.”

The researchers for this study plan to continue work on dimethyl celecoxib, an inactive form of the drug, to potentially slow or stop aortic stenosis.