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Some NSAIDs May Raise Heart Attack Risk

People taking high daily doses of ibuprofen or diclofenac may have an increased risk of heart attack and stroke, according to a new study examining the effects of COX-2 inhibitors and traditional non-steroidal anti-inflammatory drugs (NSAIDs).

The study, by Oxford researchers, comprises a meta-analysis of clinical trials, published in the British Medical Journal and reported by BBC News.

The clinical trials included comparisons of selective COX-2 inhibitors versus placebo, or selective COX-2 inhibitors versus a traditional NSAID (ibuprofen, diclofenac or naproxen), with data about heart attack, stroke, or vascular-related death. COX-2 inhibitors are a subset of the NSAID drug category.

Ibuprofen, diclofenac and naproxen are NSAIDs that are commonly used by people with chronic pain, such as pain associated with arthritis.

High-dose diclofenac (63%) was associated with an increased risk of vascular events, as was high-dose ibuprofen (51%). High-dose naproxen had no such increased risk.

The absolute increased risk of COX-2 inhibitors appeared fairly moderate, with an extra three people in 1,000 experiencing an adverse event.

COX-2 Inhibitors and NSAIDs

Concern has grown in recent years about the safety of COX-2 inhibitors. Newer COX-2 inhibitors, such as Vioxx, were developed to bypass common side effects- such as gastric bleeding and ulcers - often associated with traditional NSAIDs. However, products such as Vioxx have been removed from the market over concerns about heart attack risk.

Researchers now have similar concerns about NSAIDs -particularly at higher doses. Doses of NSAIDs given to people for chronic pain conditions are often much higher than doses people use as occasional pain remedies.

Some studies have suggested that NSAIDs also pose an increased risk of heart attack and stroke, but the results of these studies have been inconsistent.

Clinical Trial

This study by Kearney et al. consisted of a meta-analysis of data from all randomised trials that recorded serious vascular events in patients taking NSAIDs.

The researchers found that people taking COX-2 inhibitors had a 42% higher risk of heart attack or stroke than those taking placebo. Similarly, the risk was increased by 51% for high-dose ibuprofen (800mg three, times daily) and 63% for high-dose diclofenac (75mg, twice daily).

In contrast, naproxen (another NSAID) was found not to be associated with an increased risk of cardiovascular events. The researchers had hypothesized that naproxen's risk would differ from that of ibuprofen and diclofenac, because of differences in how naproxen is metabolized in the body. (The plasma half-life of naproxen is around 14 hours, compared with 1-2 hours for ibuprofen and diclofenac.)

A Small Risk

Overall, the researchers pointed out, the increased risk is small: for every 1,000 patients taking a COX-2 or an NSAID, approximately three more people per year would experience a heart attack.

"With this data we now have a complete picture of the effects of COX-2s and NSAIDs," said Dr Colin Baigent, lead researcher. "The important point is that for most people who don't have a history of heart attack or stroke the risk is very small.

"These drugs are very important in helping people to control their pain and it is for patients to discuss with their doctors whether this risk is acceptable for them."

Dr Baigent added that more studies were needed on naproxen's effects of naproxen before recommendations for its use could be made.

Professor Peter Weissberg, Medical Director of the British Heart Foundation, said that evidence was increasing that taking high doses of NSAIDs raises the risk of heart attack, according to BBC News.

"However, the increased risk is small and many patients with chronic debilitating pain may well feel that this small risk is worth taking to relieve their symptoms," he reportedly said.

Sources: Heart attack risk with pain drugs, BBC News, June 1, 2006. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. Patricia M Kearney, et al. British Medical Journal, volume 332, pages 1302-1308, June 3, 2006.

Posted: June 2006