Ibuprofen stops aspirin from helping heart

PHILADELPHIA, Dec. 19 (UPI) -- Multiple daily doses of ibuprofen or Advil undermine the protective cardiac effect of a daily aspirin regimen, according to a new study from the University of Pennsylvania.

The report is published in the Dec. 20 issue of the New England Journal of Medicine.

"Very large numbers of people are taking aspirin for protection against a second heart attack or stroke, and many people are taking nonsteroidal anti-inflammatory drugs for pain relief," Dr. Garret FitzGerald, lead researcher and professor of cardiovascular medicine at Philadelphia-based university, told United Press International.

"Ibuprofen is the most commonly used nonsteroidal drug used in North America. Given the age profile of people who take aspirin for cardioprotection, probably many millions of people are taking both classes of drugs," he said. "People are inclined to think of these drugs as not being dangerous, even in a combination. Our basic message is that if you are taking low-dose aspirin for cardioprotection and you need to take something for chronic pain relief or inflammation, consult your physician. Some drugs will undermine the cardioprotective effects of aspirin."

Aspirin and NSAIDs inhibit the same enzyme, a protein called cyclooxygenase or COX. One form of the enzyme, COX-1, is essential in blood clotting. The other form, COX-2, produces molecules related to pain and inflammation in arthritis.

"Since both NSAIDs and aspirin both bind near the reactive site deep within the COX-1 enzyme, we thought that NSAIDs might physically block aspirin from reaching its target," said Dr. Muredach Reilly, co-author and an associate clinical professor of medicine. "It would not do you a lot of good to take one medication only to have another wipe out its effects."

The researchers studied how the order of dosing influenced the effects of combinations of aspirin and NSAIDs. Taking ibuprofen before aspirin prevented aspirin's effects on platelet COX-1. If patients took aspirin two hours before the ibuprofen, however, there was no problem.

Then they repeated the study, giving ibuprofen three times a day -- the way people would generally take the drug for persistent pain or inflammation. They gave aspirin two hours before the morning dose of ibuprofen each day. There was still enough residual ibuprofen from the prior evening's dose to cause an aspirin-blocking interaction.

"We know that aspirin works to protect the heart by acting as a blood thinner, that is, it prevents clotting by inactivating the enzyme that makes platelets stick together," FitzGerald said. "This study tells us that ibuprofen can prevent this from happening by denying aspirin access to the enzyme's active site."

"This is a very significant observation that we may have overlooked over many years. It makes theoretical sense that these drugs might interfere with each other," Dr. Steven Abramson, professor of medicine at New York University School of Medicine in New York, told UPI. "In terms of public health, there are many of us who are prescribing and using aspirin based on studies that never examined this potential drug-drug interaction. The aspirin studies from years ago simply did not take this into account."

The researchers did not to see an interaction with rofecoxib, sold under the brand Vioxx. As one of the newer COX-2 specific drugs, rofecoxib does not bind to COX-1 in platelets.

The interaction also was absent from combinations of aspirin and diclofenac -- Voltaren -- an older NSAID.

"There is some evidence that diclofenac binds within the enzyme somewhat differently than does ibuprofen, but the failure to interact may also reflect its preference for COX-2, its turnover or some other factor as yet to be identified," FitzGerald said.

The researchers also saw no interaction with 1,000 milligrams of acetaminophen or Tylenol. However, at this low dosage, acetaminophen is a weak NSAID.

FitzGerald plans more research on the effects of higher does of acetaminophen on aspirin.

The study was funded in part by the National Institutes of Health in Bethesda, Md., and the Bayer Corp.

(Reported by Bruce Sylvester from West Palm Beach,Fla.)