Healthy people who take nonsteroidal anti-inflammatory drugs to relieve minor aches and pains may raise their risk of dying from heart-related problems, a Danish study finds.
The American Heart Association and the U.S. Food and Drug Administration already warn people with heart disease to be cautious about taking NSAIDs, which include ibuprofen (brand named Advil, Motrin) and diclofenac.
The new study is the first to show the same kind of increased risk among people without cardiac problems, says a report in the July issue of Circulation: Cardiovascular Quality and Outcomes, published online June 8.
“Very few studies have been designed to answer the important question: Do NSAIDs also increase the cardiovascular risk among healthy people who use these drugs for minor complaints?” said lead author Dr. Emil L. Fosbol, a cardiologist at Gentofte University Hospital in Hellerup. “This study is the first to confirm that the cardiovascular risk is indeed increased when healthy individuals use some of the drugs.”
The risks for different NSAIDs — found in an analysis of national medical records of more than one million Danes from 1997 to 2005 — varied widely. Participants, whose average age was 39, who used ibuprofen had a 29 percent greater risk of fatal or nonfatal stroke, compared to those who took no NSAID.
Use of diclofenac (Voltaren and Cataflam) was associated with a 91 percent higher risk of death from all cardiovascular diseases, while rofecoxib (Vioxx) use was associated with a 66 percent increased risk. But the study found no increased risk of cardiovascular problems — indeed, a slightly lower risk of death — associated with naproxen, sold over the counter with brand names including Aleve.
For people taking the largest doses, diclofenac was associated with a doubled risk of heart attack, and rofecoxib (Vioxx) was associated with a threefold increased risk of heart attack. Vioxx was taken off the U.S. market in 2004 because of a study finding high rates of heart attack and stroke.
“These findings are completely consistent with what we have found in patients with cardiovascular disease,” Dr. Michael E. Farkouh, a clinical cardiologist at Mount Sinai Cardiovascular Institute in New York City, said of the Danish study. “Drugs that elevate blood pressure and are associated with a thrombotic [artery-blocking] effect can be harmful in patients who are otherwise healthy.”
The percentage increases in the study were large, but the absolute overall risk in otherwise healthy people was small, Farkouh said. Nevertheless, “before you take any medication, you should consult with a physician, particularly these medications,” he said.
That warning applies especially to people who exercise regularly and are thus more likely to take an NSAID for muscle and joint pain, Farkouh said. Regular use of an NSAID increases the risk not only of cardiovascular problems but also of bleeding, a known side effect of the medications, he said.
In fact, the Danish study found an increased incidence of major bleeding events, some fatal, from all NSAIDs except celecoxib (Celebrex). Celecoxib did not appear to raise the risk of coronary death or stroke either.
The Danish findings are consistent with a 2007 American Heart Association (AHA) scientific statement about the increased risk of heart attack and stroke associated with NSAID use, said Dr. Elliott Antman, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, lead author of that paper, in a statement issued Tuesday by the AHA.
“The recommendations we made were based on our best estimates from the existing pharmacological and biological research available at the time,” Antman said. “I find this new study reassuring because it endorses the recommendations we made using a large body of actual clinical evidence.”
Antman’s advice for anyone taking an NSAID regularly is that “it is advisable to discuss with your physician why it was originally recommended or prescribed, whether you need to continue taking it, and at what dose.”
It may be wise to consider alternatives, the study authors and other experts said.
“The majority of studies have shown that naproxen has a safe cardiovascular risk profile and that ibuprofen in low doses (1200 mg and below per day) also is safe in respect to the cardiovacular risk,” Fosbol said.