Another Study Cautions Use of Ibuprofen by Heart Patients Depending on Aspirin

Feb. 14, 2003 - A new study supports research released in 2001 that shows ibuprofen, used in some pain relief medicines, blocks the blood-thinning benefits of aspirin, which could be dangerous for heart patients using aspirin.

The latest study found that those taking both aspirin and ibuprofen were twice as likely to die during the study period as those who were taking aspirin alone or with other types of common pain relievers, according to the research published this week in The Lancet medical journal.

Scientists believe ibuprofen clogs a channel inside a clotting protein that aspirin acts on. Aspirin gets stuck behind the ibuprofen and cannot get to where it is supposed to go to thin the blood.

Aspirin is considered the most important medicine for heart disease. Nearly all heart patients take it every day because it prevents the clots that cause heart attacks and strokes. Ibuprofen, which is in Motrin and Advil among other brands, is widely used for arthritis and other aches and pains.

In the 2001 study it was reported that the ibuprofen that eases arthritis pain can counteract the aspirin taken to protect your heart. This study was by researchers at the University of Pennsylvania School of Medicine. The researchers studied how aspirin, taken to prevent second heart attacks, interacts with nonsteroidal anti-inflammatory drugs (NSAIDs), a group of drugs that includes ibuprofen, commonly taken to treat rheumatoid arthritis. Their findings were published in the December 20, 2001, issue of the New England Journal of Medicine.

In the latest study, scientists at the Medicines Monitoring Unit of Britain's Medical Research Council checked the medical records of 7,107 heart patients who had been discharged from hospitals between 1989 and 1997 with aspirin prescriptions and had survived at least one month after leaving the hospital.

They were divided into four groups according to their prescriptions.

The first group included those on aspirin alone.

The second were given aspirin and ibuprofen and the third group had aspirin with another pain killer, diclofenac. Ibuprofen and diclofenac both belong to a widely used class of pain relievers known as nonsteroidal anti-inflammatory drugs, or NSAIDs.

The last group included those taking aspirin with any other NSAID, such as acetaminophen, which is in Tylenol.

The researchers found that those taking ibuprofen were almost twice as likely as those taking aspirin alone to die by 1997. That meant that for every 1,000 patients treated, there were 12 extra deaths a year when ibuprofen was taken with aspirin.

For heart-related deaths, ibuprofen was linked to three extra deaths per 1,000 patients treated per year.

Experts say it is important to track both heart-related deaths and deaths in general because deaths are sometimes attributed to the wrong cause and heart-related cases may be missed. For instance, a death certificate may say the person died in a car crash when, in fact, a heart attack or stroke at the wheel caused the crash.

No extra deaths were seen in the groups taking the other types of NSAIDs.

"The message here is beginning to be 'go for something other than ibuprofen,'" said Garret FitzGerald, who was not connected with the latest study, but whose research sparked concerns about the combination just over a year ago.

"Mechanistically, you have a very clear rationale for why it should happen," said FitzGerald, professor of cardiovascular medicine and chair of pharmacology at the University of Pennsylvania. "Now we have four studies each coming out with the same message. It's several pieces of ancillary evidence that when assembled are more persuasive than when taken in isolation."

"Lots of people take these two kinds of drugs chronically and probably a large number take both together chronically," FitzGerald said. "Talk to your doctor before you embark on this combination thinking that it's totally innocuous because both are available over the counter."

Dr. Tom MacDonald, who led the Lancet study, said taking the odd ibuprofen for a few days would not be a problem. It's regular use that seems to be at issue.

But the findings are not rock solid, experts said.

"This definitely raises a red flag ... but I don't think this can be viewed as the definitive answer on the question," said Dr. Veronique Roger, head of cardiovascular research at the Mayo Clinic in Rochester, Minn., who was not connected to the study.

It could be that heart patients who take ibuprofen have additional conditions that in turn make them more prone to premature death and were not accounted for in the study, she noted.

Garret A. FitzGerald, MD, Robinette Professor of Cardiovascular Medicine, chair of the Penn Department of Pharmacology, and director of the Penn Center for Experimental Therapeutics, said of the 2001 research, “Our findings have shown that multiple daily doses of ibuprofen can undermine the cardioprotective effects of a daily aspirin regimen. NSAIDs and aspirin are two of the most frequently consumed drugs in North America and, since people commonly take both drugs daily, it is important to see how they could interact.”

Parts of this report came from the Associated Press