A new international study finds that popular painkillers or anti-inflammatories knows as NSAIDs can increase the risk of heart attack or stroke by a third, with some having a much stronger effect than others, and size of dose also making a difference. However, experts urge patients worried about the findings not to give up on their NSAID medication and to speak to their doctor about their concerns.

Researchers from Hull York Medical School (HYMS), a joint venture between the Universities of Hull and York and the NHS in the UK and the Institute for Clinical Evaluative Sciences in Canada, systematically reviewed 51 large scale studies of non-steroidal, anti-inflammatory drug (NSAID) conducted in Europe, USA, Canada and Australia. Their findings are published online this week the journal PLoS Medicine.

They found that patients with heart problems who used NSAIDs, including diclofenac and indomethacin, had a significantly higher risk of serious cardiovascular events such as heart attack and stroke compared to patients who did not.

Even in doses available over the counter without a doctor’s prescription, diclofenac could raise someone’s risk of heart attack or stroke, they said.

However, other common NSAIDs, including naproxen and low doses of ibuprofen do not appear to be linked to an increase in risk.

Lead researcher Dr Patricia McGettigan from HYMS told the press that:

“NSAIDs provide pain relief for millions of patients with chronic inflammatory disorders. The cardiovascular risk is well described but often overlooked. In choosing which one of the many available NSAIDs to use, patients and doctors would benefit from knowledge of the balance between benefit and harm for individual NSAIDs.”

Many people use NSAIDs in both over the counter and prescription form for pain relief and for their anti-inflammatory effects to treat conditions such as headache, arthritis, back pain, gout, and the aches and fever of flu.

In 2010 in England alone, GPs wrote out nearly 17 million prescriptions for NSAIDs, that is one for every three people in the country. Of these, nearly 6 million, more than a third, were for diclofenac; 5 million were for ibuprofen and 3 million were for naproxen. All of these can also be bought without a prescription.

The researchers found that for the most commonly used NSAIDs, the highest risk was seen with diclofenac, which overall was linked to an increased risk of 40% for a cardiovascular event like a heart attack or stroke, compared with non-use.

This means that for a person with a 5% or more background risk of a cardiovascular event (typically someone with diabetes, a history of heart problems and high blood pressure), taking diclofenac would most likely increase that risk to over 7%, explained McGettigan:

“In other words, one in 50 such patients might suffer an avoidable heart attack. This is important information in making choices, particularly if there is a safer alternative,” she added.

In contrast, a healthy young person with an annual risk of heart attack or stroke of under 0.1% will experience a negligible increase in risk from taking any of the commonly used NSAIDs, said McGettigan.

The researchers found that the lowest risks were with naproxen and low doses of ibuprofen: they weren’t linked to increased cardiovascular risks. But, they did find when ibuprofen daily doses exceeded 1200 mg a day, it was linked to an 80% higher risk.

For diclofenac the link was there at both high and low dose: with a near doubling of increased risk at the higher dose.

The safest NSAID, as far as effect on cardiovascular risk is concerned, appears to be naproxen. Neither low nor high doses of this were linked to increased risk.

The researchers also looked at the newer types of NSAIDs, the Cox-2 selectives; these are available only on prescription. They found these newer NSAIDs are also linked to raised cardiovascular risks.

For instance, Rofecoxib, which was taken off the market worldwide in September 2004 because of its cardiovascular risks, was linked to an increase in risk of 45%.

Of the newer NSAIDs on the UK market, the researchers found that celecoxib was tied to an increase in risk at both low and high doses and etoricoxib appeared to raise risk more than celecoxib.

Indomethacin, an old NSAID that is still popular for the treatment of gout, was linked to a raised cardiovascular risk of 30%. The drug also has other side effects, which together with this new finding should make its clinical use even more questionable, said the researchers.

One of the drawbacks of NSAIDs is that they raise the risk of gastrointestinal ulcers, which can be reduced by taking anti-ulcer drugs like omeprazole. But you can’t do this for the cardiovascular risk, so this is another reason why it is important to have these comparisons to hand when giving patients advice, said McGettigan.

“New NSAIDs like celecoxib were developed to have a much lower risk of gastrointestinal ulcers compared with older drugs like ibuprofen, diclofenac and naproxen. They achieved this, but as the review finds, they do not have lower cardiovascular risks,” she warned.

The British Heart Foundation (BHF) urged patients who are already taking NSAIDs and are worried by these findings not to simply give up on their medication.

“As with any medicine there are benefits and potential risks to taking painkillers,” said Doireann Maddock, Senior Cardiac Nurse at BHF, “You should always speak to your doctor first because the benefits may well outweigh the risks for you.”

She explained that we have known for some time that certain painkillers are risky for heart patients and the findings of this new study should not be ignored.

“But scientists and drug regulators will need to delve deeper before we draw any firm conclusions about these drugs and their side effects,” she said.

Written by Catharine Paddock PhD
Courtesy: Medical News Today

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