Ibuprofen claimed to raise cardiac arrest risk by a ...

"Taking common painkillers like ibuprofen 'increases your risk of cardiac arrest by a THIRD'," The Sun reports.

Researchers found a link between the potentially fatal heart problem and ibuprofen use, as well as another type of non-steroidal anti-inflammatory drug (NSAID) called diclofenac. A cardiac arrest is a serious emergency where the heart stops pumping blood around the body.

The Danish study looked at 29,000 people who experienced a cardiac arrest, and then at whether these people had taken NSAIDs.

The researchers found the risk of a cardiac arrest was increased by a third for those who took ibuprofen in the 30 days leading up to cardiac arrest.

The risk was doubled for those taking diclofenac, which is only available on prescription in the UK. There was no evidence of an increased risk for other NSAIDs.

But the underlying biological reasons for this link weren't discussed in the study, so it's not clear what might cause this increased risk of cardiac arrest.

It's also possible some people were taking NSAIDs because they had symptoms of a pre-existing (possibly undiagnosed) condition that could increase the risk of cardiac arrest, such as heart disease.

An alternative painkiller to try is paracetamol, or you could try physiotherapy for things like joint and muscle pain. Get advice from your pharmacist or GP on the most suitable treatment for your symptoms.

Where did the story come from?

The study was carried out by researchers from institutions in Denmark, including Copenhagen University Hospital, Aalborg University and the University of Southern Denmark.

It was funded by the European Regional Development Fund, the Novo Nordisk Foundation, and TrygFonden, a foundation that promotes public health. The authors declared no conflict of interest.

The study was published in the peer-reviewed European Heart Journal on an open access basis, so it's free to read online.

Generally, the media coverage of the study was accurate, although The Sun inaccurately claimed that, "Ibuprofen – the most common NSAID – increased that risk by a staggering 50 per cent".

This isn't actually the case – ibuprofen accounted for 51% of total NSAID use, but was found to increase risk by 31%, not 50%.

What kind of research was this?

This observational case-time-control study looked at data from the Danish nationwide registries to find out if there's a link between using NSAIDs and an increased risk of having a cardiac arrest outside of hospital.

A cardiac arrest is when the heart suddenly stops pumping blood around the body. The person will usually fall unconscious and stop breathing. It's not the same as a heart attack, although a heart attack can lead to cardiac arrest.

A case-time-control study is good because the same individual is both the case and the control in two different periods of time. This means confounding variables like pre-existing illnesses remain the same when comparing the two groups.

What did the research involve?

This study involved a case-time-control design, including all people aged 10 and above who had a cardiac arrest outside hospital where efforts were made to resuscitate them between 2001 and 2010, as identified by the Danish Cardiac Arrest Registry.

The case-time-control design meant each person was both the case and the control in different time periods. Their exposure to NSAIDs was assessed in both the case and control periods.

They were in the case period in the 30 days before their cardiac arrest and the control period was a preceding 30-day period, when they didn't experience a cardiac arrest event. There was a 30-day "wash out period" in between the control and the case times.

NSAID exposure was assessed by looking at prescribing patterns for the most commonly used NSAIDs in Denmark. These were diclofenac, naproxen and ibuprofen, as well as two COX-2 selective inhibitors, rofecoxib and celecoxib.

The researchers only included people in the analysis who requested a prescription in the case period, but not during the control period.

Information on other existing illnesses was obtained from discharge diagnoses from hospital admissions up to five years before the cardiac arrest.

One problem is that prescribing patterns change over time in the general population, but the study accounted for this by using a control group from the general population to adjust for these changes.

What were the basic results?

The analysis identified 28,947 people who experienced an out-of-hospital cardiac arrest between 2001 and 2010.

In the case period, 3,376 people had been treated with an NSAID in the 30 days leading up to cardiac arrest.

Ibuprofen was the most commonly prescribed NSAID, accounting for 51% of total NSAID use, followed by diclofenac, which accounted for 21.8% of total use.

The main findings were:

use of any NSAID increased risk of cardiac arrest by 31% (odds ratio [OR] 1.31, 95% confidence interval [CI] 1.17 to 1.46)
use of ibuprofen increased risk of cardiac arrest by 31% (OR 1.31, 95% CI 1.14 to 1.51)
use of diclofenac increased risk of cardiac arrest by 50% (OR 1.50, 95% CI 1.23 to 1.82)
use of naproxen was not associated with cardiac arrest, nor was use of COX-2 inhibitors

NSAID users were more likely to be women, have less cardiovascular disease, but be more likely to have cancer and rheumatic diseases. They were also more likely to be treated with psychiatric medication, diuretics and morphine.

How did the researchers interpret the results?

The researchers concluded that, "In a nationwide cohort of persons with OHCA [out-of-hospital cardiac arrest], we found that short-term treatment with non-selective NSAIDs, particularly ibuprofen and diclofenac, was associated with an increased early risk of cardiac arrest.

"We found no association between cardiac arrest and use of the COX-2 selective inhibitors, rofecoxib and celecoxib, nor the non-selective NSAID naproxen."

They went on to say: "Our findings support the accumulating evidence of an unfavourable cardiovascular risk profile associated with use of the non-selective NSAIDs. This calls for special awareness in order to balance risks against benefits in treatment with NSAIDs."

Conclusion

This study showed an association between taking ibuprofen or diclofenac and an increased risk of a cardiac arrest in the following 30 days, but no association was found with the other NSAIDs investigated.

But this study does have its limitations:

Although the researchers used the same people to avoid confounding variables, the same person will differ in certain aspects over time – for example, certain diseases may get better or worse, which might have affected the results.
The study only looked at prescribed drugs and not over-the-counter drugs. In Denmark, ibuprofen was the only over-the-counter drug sold at the time of the study and therefore a large number of people taking ibuprofen might have been missed.
It could be that people are taking NSAIDs for other underlying problems that increase the risk of cardiac arrest, so it might be these problems increasing risk of cardiac arrest, not the NSAIDs.
The dose and duration of NSAIDs might have varied across participants. It's not clear whether the greater the dose or duration, the higher the risk of cardiac arrest.
The study was carried out in Denmark – the findings might not be as relevant to other populations, who have different lifestyles.

The Guardian carries a quote from the lead author of the study, Professor Gunnar Gislason, warning: "The findings are a stark reminder that NSAIDs are not harmless … [and] should be used with caution and for a valid indication.

"They should probably be avoided in patients with cardiovascular disease or many cardiovascular risk factors."

If you're unclear about whether you should be taking NSAIDs, ask your GP or pharmacist for advice.