Painkillers linked to heart attack risks

Anti-inflammatory drugs are widely used to manage pain in patients with conditions such as osteoarthritis Reuters

Taking certain commonly used painkillers for long periods or in high doses increases the risk of heart attacks or strokes, a study has suggested.

This content was published on January 16, 2011 - 20:33

The report by researchers from Bern University, published in the British Medical Journal, looked at 31 clinical trials on more than 116,000 patients to examine the effects of painkillers on people’s health.

The team studied data from existing large-scale studies comparing use of non-steroidal anti-inflammatory drugs (NSAIDs) as well as new-generation anti-inflammatory medicines (COX-2 inhibitors) – naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib and lumiracoxib – with other drugs or placebos.

Anti-inflammatory drugs are widely used to manage pain in patients with osteoarthritis and other painful conditions.

“There is little evidence to suggest that any of the investigated NSAIDs included in these studies are safe in cardiovascular terms,” Peter Jüni, professor of clinical epidemiology at Bern University, told

While the absolute risk of cardiovascular problems among people taking painkillers was low, the team found that relative to a placebo the drugs carried "important risks".

The scientists found that compared with a placebo or dummy pill, rofecoxib and lumiracoxib were associated with twice the risk of heart attack, while ibuprofen was associated with more than three times the risk of stroke.


Etoricoxib and diclofenac were linked with around four times the risk of cardiovascular death. Naxproxen seemed the least harmful, but should be weighed against potential side effects including stomach problems, they noted.

“Underestimated” risks


Jüni stressed that the findings did not relate to people taking anti-inflammatories occasionally for symptoms such as period pain or sports injuries.

The problematic patients are typically elderly people who may be obese with high cholestoral levels or hypertension or have musculoskeletal conditions like osteoarthritis, and be using the drugs “chronically”.

Without drugs, such people have a one per cent risk over one year of heart attack or stroke, but when taking NSAIDs, the risk is up to four per cent, Jüni said.

“I still think the risks are underestimated by the medical profession,” he said. “Many patients are not aware of the issues. I think more information is necessary. It would be reasonable to have more prominent warnings so people take the drugs now and again rather than daily and not several times a day.”

No immediate changes


But the Swiss Agency for Therapeutic Products (Swissmedic), responsible for checking drug compliance, believes drug information for painkillers is “prominent, detailed and clear”.

And it does not envisage making any immediate changes in the light of this study.

“Discussions about the analysis and results first have to be carried out among experts and regulators at the scientific level,” said Swissmedic spokesman Joachim Gross.

Several groups of researchers became concerned about the toxicity issue from 2001 onwards but this was largely ignored by the medical community, Jüni said.

In 2004, Vioxx, a  COX-2 inhibitor, was withdrawn from the market after a trial showed it increased the risk of heart disease.


The researchers said that since then there has been much debate about the heart safety of COX-2 inhibitors and NSAIDs, but various studies have failed to give clear results.



Commenting on the findings, Simon Maxwell, a professor of clinical pharmacology at Edinburgh University, said it was important to see them in context.

"Most users of these drugs will only take them for a relatively brief duration to treat short-lasting episodes of pain and are at minimal risk," he said.


He added that patients with chronic pain may need to use painkillers for longer periods and while the study suggested they might be exposed to some excess risk, the alternatives "may be less acceptable".

Professor Bernhard Meier, chief cardiologist at Bern's Inselspital Hospital, echoed this, adding that patients often faced a dilemma.

“When it’s necessary to take medication like Voltaren or Naproxen, then [patients should] continue to do so, but try to reduce the dose and see if it’s possible to go without,” he told Swiss national television.


The drugs studied were traditional non-steroidal anti-inflammatory drugs (NSAIDS) as well as new-generation anti-inflammatory medicines known as COX-2 inhibitors.

They included naproxen, ibuprofen, diclofenac, Pfizer's Celebrex, or celecoxib, Merck's Arcoxia, or etoricoxib, Merck's Vioxx, or rofecoxib and Novartis' Prexige, or lumiracoxib.

All are available in Switzerland, with the exception of lumiracoxib and rofecoxib. Ibuprofen and diclofenac are both available over the counter in Swiss chemists but at lower doses.

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Strokes are caused by disruption of the blood supply to the brain.

This may result from either blockage (ischaemic stroke) or rupture of a blood vessel (haemorrhagic stroke).

Risk factors include high blood pressure, atrial fibrillation (a heart rhythm disorder), high blood cholesterol, tobacco use, unhealthy diet, physical inactivity and diabetes,

(World Health Organization)

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