Common painkilling non-steroidal anti-inflammatory drugs are linked to a higher risk of serious cardiovascular problems, such as heart attacks, in some individuals, new research has found.
One particular drug, diclofenac, has similar risks to Vioxx, an NSAID that was pulled off the market in 2004 due to concerns over cardiovascular problems. Ibuprofen and naproxen were found to have the lowest risk profile in the new study.
The results, published this week in the journal PLoS Medicine, should convince clinicians to avoid riskier drugs, such as diclofenac, said study co-author David Henry.
"Doctors and patients need to be aware of the evidence," said Dr. Henry, president and CEO of Toronto's Institute for Clinical Evaluative Sciences.
NSAIDs are a class of widely prescribed drugs used to treat conditions such as osteoarthritis and rheumatoid arthritis, and researchers have begun to scrutinize them much more closely in the wake of the Vioxx market withdrawal.
The new study helps cement the idea that many of them may be problematic, particularly if the individual has a pre-existing history ofheart problems or other health issues that boost the chances of heart attacks or strokes.
"The important thing to say is that for the majority of people who use these drugs, they don't need to really be concerned because the risks aren't that high," Dr. Henry said. "It's just that for some people, that relative increase in risk is important."
The new study was not conducted using data from randomized-controlled trials, where patients are randomly assigned to receive a particular treatment and compared against a group receiving a different treatment or placebo.
Instead, researchers examined data from a group of previously conducted observational studies, which they described as a high-quality method of gathering information about the effects of NSAIDs on patients over time.
Although randomized-controlled studies are often considered the best type of trial, the ones that have focused on NSAIDs used by patients are either too small or are limited in scope, making it difficult to draw conclusions about risks facing the general population, the researchers said.
The observational studies allowed researchers to analyze real-world effects of a wide variety of NSAID medications.
They found that diclofenac was linked to the highest cardiovascular risks, comparable to problems observed in patients taking Vioxx. The drug, sold under a variety of brand names including Voltaren, is considered the most widely prescribed NSAID in the world.
Although the drug is used widely in Canada, other NSAIDs are more common. In Canada, about 1.3 million prescriptions for diclofenac were dispensed from retail pharmacies in 2009, according to IMS Brogan, a firm that tracks the drug industry. About 3.3 million prescriptions for naproxen, sold under such names as Aleve, were filled at pharmacies in 2009 and 1.4 million for ibuprofen, also known as Advil and Motrin. Those drugs had the lowest risks; ibuprofen only posed problems when given in high doses of more than 1,200 milligrams a day.
About 2.5 million prescriptions were filled in 2009 for celecoxib, sold under the brand Celebrex. Some studies have indicated the drug may pose heightened risk to patients even at low doses, the study said.
The risks of diclofenac represent significant concern and the researchers say they hope the findings will lead to the phase-out of prescribing the drug.
"[We]got a risk we couldn't distinguish from Vioxx, which was taken off the market," Dr. Henry said. "Regulatory agencies don't seem to be acting against [diclofenac]"
The researchers also that noted several drugs that haven't been studied extensively may also pose serious risks. Etoricoxib (not approved in Canada), etodolac (sold under such names as Apo-Etodolac) and indomethacin (sold under such names as Apo-Indomethacin) all seemed to elevate the chance of cardiovascular events, although more research is needed.
Andreas Laupacis, executive director of the Li Ka Shing Knowledge Institute of St. Michael's Hospital in Toronto, noted that NSAIDs have likely been associated with cardiovascular problems for decades, but that the risks are only coming to light as a result of Vioxx.
Problems with Vioxx emerged after large studies were conducted. But NSAIDs have never been subject to such sweeping scrutiny, which may have allowed the risks of some drugs to go unnoticed, Dr. Laupacis said.
"I think we were lulled into thinking they didn't have any negative cardiovascular effects largely because the studies haven't been done," he said.
Now that the heart risks are becoming more known, the information poses a new problem for doctors, Dr. Laupacis said. That's because some NSAIDs come with a higher risk of gastrointestinal problems, such as bleeding, meaning the risks of painkilling drugs in that class need to be carefully weighed against each other.
"I think this is kind of about a tailoring of risk," Dr. Laupacis said.