Long-Term Painkillers Increase Risk Of Heart Attack

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 when it comes to this.

These pain relieving drugs known as non-steroidal anti-inflammatory drugs — or NSAIDs for short — are used by millions of people worldwide for relieving their long-term pain from several different things, such as from conditions like arthritis.

What is this study all about?

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

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

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

When it comes to the the general population, the risk of this type of event is about 8 in 1000 people, so in the population of people studied in this particular study it would be an additional three, making it a total of 11 people in 1000.

All of the NSAIDs studied were found to double the risk of heart failure in patients.

One good finding in this study was that the NSAID which is called naproxen was actually not associated with any of the increased risk factors for cardiovascular events or related deaths. This means that if you must take an NSAID, naproxen is a good choice for you. 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, for other reasons.

Is the cardiovascular connection completely unexpected?

No. It has been known for some time that NSAIDs may bring on untoward health events because of their negative effects on blood vessels. In 2004 there was a 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). 

So Why Is The Cardiovascular Connection Unexpected?

The two withdrawn NSAIDs are known as ‘coxibs’ and they belong to a class of medications known as cyclo-oxygenase 2 (COX-2) inhibitors. So the risk of cardiovascular side effects was originally just associated with these particular drugs. But diclofenac and ibuprofen are in a slightly different class, so the latest research shows that a wider group of NSAIDs are associated with cardiovascular risks.

How do NSAIDS work and what is the significance of COX-1 and 2?

NSAIDs prevent the production of substances called prostaglandins which are released when the body is injured or in response to diseases such as arthritis.  

There are two pathways in the production of prostaglandins, which are controlled by production of COX-1 and COX-2 enzymes. 

The earliest NSAIDS (such as ibuprofen and diclofenac) inhibited both types of COX enzymes and because of their effect on COX-1 enzymes they are associated with adverse effects in the digestive tract.  These effects include ulceration (wearing away of the gut lining) and bleeding from ulcers.  As a result, NSAIDs which were selective and only blocked COX-2 enzymes, were developed. 

This was thought to be a significant step forward at the time (the 1990s) because these selective COX-2 inhibitors were as effective in relieving pain and inflammation as the non-selective earlier ones. But they were not as bad as the typical NSAID for causing side effects affecting the digestive tract.  However as mentioned, they later became associated with cardiovascular disease instead.

Should I stop taking NSAIDs like ibuprofen for aches and pains?

The latest study was of high-doses of NSAIDs prescribed by doctors.

Also, the study was of people who took these drugs long-term i.e. every day for a year or more.  Taking the occasional ibuprofen tablet for headache or joint pains does not involve the same risks.

What should people who take long-term high-dose NSAIDs do?

Talk to their doctor. One conclusion of the study was that the risk of serious side effects from these drugs is predictable. This will enable doctors and patients to weigh up the potential hazards against the benefits of effective long-term pain relief.

What alternatives are there to high-dose NSAIDs?

Naproxen - the only NSAID studied which wasn’t associated with cardiovascular risks. 

Other classes of painkillers, which are not NSAIDS, include opiates which are related to morphine.  They include codeine, which is available as a single agent in various strengths, or also combined with other painkillers. A combination of acetominophen (paracetamol) with codeine is known in some places as co-codamol, and co-dydramol is paracetamol with dihydrocodeine. 

For this reason most opiate drugs are not available without a prescription.

If you are at all concerned about risks associated with medication you are taking, speak to your doctor or a pharmacist.