A recent study linked a common prescription drug that people with arthritis use to relieve pain and inflammation to a heart valve problem.
The drug, which goes by the generic name celecoxib and the brand name Celebrex, belongs to a class of nonsteroidal anti-inflammatory drugs (NSAIDs) called COX-2 inhibitors.
After analyzing thousands of electronic medical records, scientists at Vanderbilt University in Nashville, TN, found a link between specific celecoxib use and a higher risk of aortic stenosis.
Aortic stenosis is a condition that narrows the aortic valve in the heart and restricts blood flow through it. It usually results from scarring and calcification, or calcium buildup, during aging.
In lab tests, the researchers also found that treating aortic valve cells with celecoxib increased cell calcification.
Those results, now published in JACC: Basic to Translational Science, seem to contradict a 2016 NEJM to study who said celecoxib was no more risky to the heart than the older NSAIDs naproxen and ibuprofen.
However, the authors note that the previous study focused “on acute, relatively short-term, thrombotic events,” and did not examine outcomes related to valve disease, which takes longer to develop. .
“In this study,” says first author Meghan A. Bowler, Ph.D., who worked on the survey in the Department of Biomedical Engineering, “we add a long-term perspective on celecoxib use.”
Aortic stenosis is a stiffening of the valve located between the aorta and the left ventricle of the heart. The stiffening causes blood to pass less easily from the heart to the aorta, from where it then flows to the rest of the body.
Although some people have aortic stenosis due to a birth defect, the
In their study, the authors note that more than 1 in 4 people over the age of 65 in the United States have the type of aortic stenosis that develops from calcium buildup.
The disease is progressive and, in the absence of suitable medication, the only effective treatment is surgical replacement of the valve.
It was concern over the lack of effective drugs that prompted researchers to study the already approved celecoxib as a treatment for aortic stenosis.
They chose celecoxib because previous studies had suggested it might be effective against a protein called cadherin-11 that is active in calcifying aortic valve disease. These studies have shown that celecoxib binds to protein.
However, when they tested the effect of celecoxib on valve cells, the investigators found that it had the opposite result; it appears to increase calcification and other markers of tissue stiffening.
“Unexpectedly,” they note, “treatment with celecoxib led to features of myofibroblast activation and calcifying nodule formation in vitro.”
After establishing the lab result, the researchers then looked for clinical evidence. They analyzed 8,600 long-term electronic medical records for links between the diagnosis of heart valve disease and the use of celecoxib, ibuprofen and naproxen.
The analysis found that taking celecoxib was linked to a 20% increased risk of developing aortic stenosis. He found no link between aortic stenosis and ibuprofen or naproxen.
The authors conclude that “Taken together, these data suggest that the use of celecoxib is associated with the development of [calcific aortic valve disease].”
In a discussion of the limitations of the study, the scientists point to the fact that they used pig heart valves in their lab tests.
This is common practice because pig heart valves tend to be healthier than human heart cells, which are usually sourced from donors with health conditions that could influence outcomes.
They suggest that further studies should now seek to confirm these findings in humans or a variety of mouse models of heart valves.
The researchers also tested dimethyl celecoxib, which is an inactive form of celecoxib. They have found that this drug may be a safer option than celecoxib for people with aortic stenosis and intend to continue research.
“Calcification of the aortic valve can take several years. So if you are more at risk you may want to consider taking another [pain reliever] or treatment of rheumatoid arthritis.
Meghan A. Bowler, Ph.D.