NSAIDs raise risk of heart disease: Study

A new study published online in the British Medical Journal explores the relative safety of non-steroidal anti-inflammatory medications (NSAIDs), commonly used to treat joint and muscle aches and pain and concludes that NSAIDs significantly increase the risk of cardiovascular events in patients who take them regularly.

Peter Jüni head of the division of clinical epidemiology at The University of Bern in Switzerland said, “These drugs have some use in the treatment of chronic pain… But they have safety issues. In the signals we saw, there was a two- to fourfold increase in the risk of myocardial infarctions [heart attacks], stroke, or cardiovascular death, and these are, clinically, considerable increases in risk.” He noted that only 25 to 50 patients would need to be treated with NSAIDs for one year to cause one additional event such as a heart attack or stroke.

Wayne A. Ray, director of the division of pharmacoepidemiology in the department of preventive medicine at Vanderbilt University in Nashville added, “There’s a very large overlap between cardiovascular risk and the musculoskeletal symptoms that people take NSAIDs for.” A 2002 analysis of the government’s National Health and Nutrition Examination Survey, for example, found that 40% of adults with osteoarthritis, or OA, also had high blood pressure, while 32% percent had high total cholesterol. Twenty percent of people with OA reported that they smoked. “You have an 80-year-old person with a history of heart disease who has a problem with her knees. This is someone who’s at cardiovascular risk and likely to be taking NSAIDs,” says Wayne, who wrote an editorial that accompanied the study.

Painkillers have been in focus due to their heart risk. A previous study found that the painkiller Vioxx was associated with significant increases in the risks of heart attacks and strokes which led to its withdrawal from the market in 2004. Ray said, “We found, almost inadvertently, that these drugs can have cardiovascular effects. We were sort of caught without sufficient knowledge base to guide clinical practices… There are differences in the various NSAIDs and these differences might well confer differences in cardiovascular risk. We really have less information than we need about the comparative safety of these drugs.”

The study led by Sven Trelle, also at the University of Bern, collated results from 31 randomized, controlled trials. The trials included more than 116,000 patients. Using innovative statistical methods researchers compared the relative safety of different NSAID medications. The drugs were naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib and two others not used in England, called rofecoxib or Vioxx, and lumiracoxib. Overall, naproxen appeared to have the safest cardiovascular risk profile of the seven included in the review. Ibuprofen was associated with more than three times the risk of stroke, compared to a placebo. Diclofenac was associated with almost four times the risk of cardiovascular death.

A recent study published in the Dec. 15/27, 2010, issue of the Archives of Internal Medicine found that opioid users had an elevated risk of having a heart attack compared to users of NSAIDs. The same study found that opioid users had higher risks of fractures than those taking NSAIDs. Jüni said, “It is a big problem… It just points out that we don’t have a good pharmacological alternative to treat musculoskeletal pain.” So at present weight loss and exercise should be a person’s first line of defense against many kinds of joint and muscle pain say experts. Many think that topical treatments, like NSAID gels and patches, may relieve pain without as many adverse effects for the stomach and heart as pills. And experts say that for some patients, joint replacement surgery may be a good alternative. Jüni adds, “If you take them, don’t take them regularly and not daily… And if you have to take them, ideally take them once a day and not several times a day and in dosages as low as possible.”

The Proprietary Association of Great Britain (PAGB) is the UK trade association representing manufacturers of over-the-counter (OTC) medicines. Its chief executive, Sheila Kelly, said, “The studies that the researchers looked at involved people taking high doses of NSAIDs on a long-term basis, for chronic conditions such as osteoarthritis…Patients with such conditions will have their medicines prescribed by the doctor who will decide on the most appropriate treatment for them, taking into account any other risk factors…People who buy over-the-counter medicines containing ibuprofen, naproxen or diclofenac to treat the occasional headache, sprain or period pain should not be alarmed at these findings…At the dosage levels available over-the-counter, for short-term use and used according to the instructions on pack, these medicines are extremely safe.”

This study was funded by the Swiss National Science Foundation.

Dr. Ananya Mandal

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.

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