Features April 2010 Issue

Celecoxib May Offset Benefits of Aspirin in Preventing Blood Clots

New studies indicate that the arthritis pain drug may interfere with protective properties of low-dose aspirin among older adults.

Add celecoxib (Celebrex) to the list of medications that may counter the effects of small, daily doses of aspirin used by millions of Americans to reduce the risk of heart disease and stroke.

"There is evidence from laboratory testing that many arthritis drugs including naproxen (Naprosyn), ibuprofen (Motrin), and celecoxib (Celebrex) interfere with the blood-thinning effect of aspirin," says Steven

Aspirinís blood-thinning action can be weakened by celecoxib as well as other arthritis pain relievers.

E. Nissen, MD, Chairman, Department of Cardiovascular Medicine at Cleveland Clinic. "However, this has never been confirmed in prospective randomized trials." A study published in the January 2008 issue of the Journal of Clinical Pharmacology confirmed previous research that ibuprofen undermines aspirinís ability to act as an anti-platelet agent.

New Studies Confirm

Now two new studies, one conducted at the University of Michigan and the other at Ben-Gurion University of the Negev in Israel, indicate that middle-aged and older patients who take aspirin to limit the risk of heart attack and stroke may not be getting the protection they seek because celecoxib prevents aspirin from doing its anti-clotting job. The results of the studies were published in the Dec. 1, 2009 online edition of Proceedings of the National Academy of Sciences.

At the Michigan School of Medicine, William L. Smith, PhD, senior author and a professor of biochemistry, found in test-tube and animal studies that celecoxib interferes with aspirinís ability, taken in low doses, to discourage blood clots. Celebrex is the only coxib currently approved for use in the U.S.

Dr. Smith and his colleagues used biochemical measurements and X-ray technology to discover that celecoxib binds to an enzyme that promotes clotting, thus slowing aspirinís action.

Greatest Risk

"The greatest risk," says Dr. Smith, "is having people take celecoxib who are taking aspirin for cardiovascular problems that are known to be mitigated (made less severe) by aspirin, including patients with unstable angina or those at high risk for a second heart attack." Approximately 50 million Americans take a daily dose of baby aspirin, which is 81 milligrams.

Professor Gilad Rimon of the Department of Clinical Pharmacology at Ben-Gurion University, reached a similar conclusion based on his universityís research. "Our findings strongly suggest that humans who are consuming coxibs and a low dose of aspirin simultaneously are exposed to a greater risk of cardiovascular events."

Dr. Smith points out that previous studies on healthy subjects found no effect on blood clotting when celecoxib was combined with aspirin at higher doses (324 mg). However, if this protocol were to be carried out, the long-term adverse effect of aspirin on the gastrointestinal tract would have to be taken into account.

He also acknowledges that what happens in laboratory and animal studies may not occur among humans, and that his studies need to be replicated in humans before definitive conclusions can be made.

Spacing Medications

"Most clinicians do not alter their choice of arthritis drugs in patients who take aspirin," says Dr. Nissen. "One approach that has been advocated is to take aspirin one hour before taking arthritis medicine, which may lessen any potential interference with aspirinís effect."

The two current studies are compelling enough to get the attention of the medical community. If they havenít already, it may be time for doctors and patients to consider alternatives to the celecoxib/aspirin combination or find ways to arrange the timing of counterproductive medications so that the patient can get both pain relief and some degree of protection against heart attack and stroke.