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A study has found that taking high-dose painkillers such as ibuprofen and diclofenac long-term could increase risk of heart attack by about a third. Are these drugs all the same, how do they work, are they ever safe to take and are there alternatives?

A recently-published study has shown that people who take simple painkillers such as ibuprofen or diclofenac for long-term pain relief, have a greater risk of having a heart attack, stroke or dying from such an event. People who smoke or are obese are particularly at risk.

These pain-relieving drugs known as non-steroidal anti-inflammatory drugs (NSAIDs) are used by millions of people worldwide for relief of long-term pain, such as from conditions like arthritis.

What is this study all about?

The study analyzed data from 280 studies which compared NSAIDs with placebo.  They also analysed 474 trials comparing ibuprofen and diclofenac (both of which are NSAIDs).  The data were from  over 30,000 people and recorded the number of cases of heart attack, stroke, cardiovascular events, death, and bleeding from the digestive tract (a common side effect of NSAIDs).

How much of a link between NSAIDs and cardiovascular events was found?

The study showed that for every 1000 people taking one of the painkilling drugs for a year, an additional three would have a serious event related to blockage of a blood vessel, either in their heart or their brain i.e. a heart attack or stroke. (This was compared to patients who were treated with placebo).  Of these three people, one of them would die as a result of this event. 

In the general population the risk of this type of event is 8 in 1000 people, so in the population of people studied there would be an additional 3, making a total of 11 people in 1000.

This means that an additional 38% would have a heart attack or stroke as a result of taking long-term pain medication.

All of the NSAIDs studied doubled the risk of heart failure.

One good finding was that the NSAID called naproxen was not associated with any increased risk of cardiovascular events or related deaths.  Also, although there were more side effects and deaths in the ibuprofen-treated people, this did not reach a statistically significant level. This means that it did not happen often enough to be taken as proof - it could just have occurred by chance.

The bad news is that all of the NSAIDS were associated with adverse effects in the digestive tract – this included ibuprofen and naproxen.

Is the cardiovascular connection completely unexpected?

No.  It has been known for some time that NSAIDs may bring on untoward events because of their effects on blood vessels. In 2004 there was worldwide voluntary withdrawal by the manufacturer (Merck, Sharp and Dohme) of their product Vioxx and Vioxx Acute (rofecoxib) and in 2005 the FDA asked Pfizer to withdraw its prescription NSAID, Bextra (valdecoxib). 

In both cases the withdrawals were because of concerns that the risk of cardiovascular side effects outweighed the benefits of the drugs.
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