02/12/2013 05:01 EST | Updated 04/14/2013 05:12 EDT

Arthritis pain drug should be pulled due to adverse heart effects: study

TORONTO - Researchers are calling for the removal of a widely used pain medication from worldwide markets due to a high risk of heart attack and other adverse cardiovascular events associated with the drug.

Diclofenac, a non-steroidal anti-inflammatory drug, or NSAID, is often prescribed for relieving the pain and inflammation of arthritis.

But the researchers say diclofenac, which is sold under a variety of brand names, including Voltaren in Canada, carries an almost identical risk of serious cardiovascular side-effects as Vioxx.

Vioxx was a highly touted and highly promoted NSAID that ended up being pulled from the market by its maker, Merck, after a patient trial showed it was linked to an increased rate of heart attacks and strokes.

"This is a drug that should be taken off the market, it needs to go," Dr. David Henry, CEO of the Institute for Clinical Evaluative Sciences (ICES) in Toronto, said Tuesday of diclofenac.

"This drug increases the risk of heart attack by about the same degree as Vioxx did. And Vioxx was withdrawn from world markets in 2004 by the manufacturer because of that risk," said Henry, who has a background in clinical pharmacology and has studied NSAIDs for about two decades.

"So this drug is still there, very widely used, and internationally the most popular drug despite having an almost identical cardiovascular risk profile to a drug that was taken off the market eight years ago."

In a paper published in this week's edition of PLoS Medicine, Henry and co-author Dr. Patricia McGettigan of the London School of Medicine and Dentistry outline the cardiovascular risks of various anti-inflammatory painkillers, based on an analysis of numerous studies.

They found that people taking diclofenac have a 40 per cent higher risk of having a heart attack than those taking naproxen, considered the safest NSAID choice for minimizing cardiovascular risk.

For people with underlying heart disease, taking diclofenac significantly raises the risk of heart attack, said Henry.

Health Canada said it is aware of the study and is reviewing its findings as part of ongoing monitoring of NSAID safety.

"Before commenting any further on the study or its conclusions, Health Canada scientists will review both the data used for the study and the methodology used to analyze the data that led to the authors' conclusions," a spokesman said by email.

"Health Canada will continue to review all available new information regarding the safety of NSAIDs, including diclofenac products and cardiovascular adverse events."

Novartis is one of many Canadian generic and brand-name pharmaceutical companies that sells diclofenac in various forms. Among its products are diclofenac tablets and topical gel marketed under the brand name Voltaren.

The drug maker said it welcomes researchers' assessments of therapies in the interest of patient safety, and noted that diclofenac is being comprehensively reviewed by a committee of the European Medicines Agency.

"Novartis fully supports this review and remains confident that the information available to date does not change the favourable benefit/risk profile of diclofenac when used as directed," the company said by email.

On a website for Voltaren Gel, its over-the-counter skin preparation for relieving joint pain, Novartis outlines the potential risks of all NSAIDs, warning that they "may increase the chance of a heart attack or stroke that can lead to death. This chance increases with longer use of NSAID medicines (and) in people who have heart disease."

While diclofenac racks up a respectable proportion of NSAIDs sold in Canada, the U.K. and Australia, the researchers' biggest concern is about low- and middle-income countries in Asia and South Asia, where the drug commands a huge market share.

"What ... we wanted to know was how extensively it was used in those countries that now are experiencing a major epidemic of cardiovascular disease," said Henry, pointing to such countries as China and India.

"We're talking about vast populations where this drug and others are available very cheaply and are widely used. And we wanted to know whether these high-risk drugs — diclofenac's not the only one, there's an equivalent drug called etoricoxib — are still being used.

"Between them, they have a third of the entire market," he said, noting that etoricoxib is not sold in North America.

In China, for instance, diclofenac is the most commonly used NSAID in hospitals and its popularity has huge public health implications, the authors say.

"If it were taken by only one per cent of China's population of approximately 1.3 billion annually, based on the relative risk calculations ... it could cause 14,000 additional unintended deaths," they write.

"These deaths are preventable — lower-risk NSAIDs, including naproxen and low-dose ibuprofen, are widely available and are equally efficacious. Both are available as generic products."

The researchers have been raising a red flag about diclofenac in medical journal studies for several years, but regulatory agencies in countries around the world have been slow to label the drug as being high-risk.

In fact, many countries continue to keep it on their essential medicines lists, which encourages doctors to continue prescribing the drug despite evidence of its risks to heart health.

In New Zealand and Bangladesh, for instance, diclofenac makes up 43 per cent of all NSAIDs sold. In Canada, the drug has a 17 per cent market share.

Henry said the researchers have petitioned the World Health Organization to list naproxen as the preferred NSAID, based on its safer cardiovascular side-effect profile.

"And hopefully that will affect the pick-up in the essential medicines lists which are developed in each of the countries," he said.