Diclofenac and ibuprofen are associated with increased risk of cardiac arrest
BMJ 2017; 356 doi: https://doi.org/10.1136/bmj.j1358 (Published 16 March 2017) Cite this as: BMJ 2017;356:j1358
Use of the non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac and ibuprofen are associated with a significantly increased risk of cardiac arrest, a large Danish study has found.
The authors of the study, which was reported in the European Heart Journal: Cardiovascular Pharmacotherapy,1 said that the findings were a stark reminder that NSAIDs were not harmless and should only be used after consulting a healthcare professional.
The researchers used the Danish Cardiac Arrest Registry to identify everyone who had a cardiac arrest out of hospital between 2001 and 2010. Of the 28 947 people identified, 3376 were treated with an NSAID up to 30 days before their cardiac arrest. Each case was matched with four controls from the Danish Patient Registry.
Ibuprofen and diclofenac were the most commonly used NSAIDs and represented 51% and 22% of total NSAID use, respectively. The study found that use of any NSAID was associated with a 31% increased risk of cardiac arrest. Diclofenac was associated with a 50% increased risk (odds ratio 1.50, 95% confidence interval 1.23 to 1.82), and ibuprofen was associated with a 31% increased risk (1.31, 1.14 to 1.51) of cardiac arrest.
The study found no significant association between cardiac arrest and the COX 2 selective inhibitors celecoxib and rofecoxib, nor with the unselective NSAID naproxen. However, these drugs are rarely used in Denmark and so relatively few events occurred, leading to low statistical power.
One limitation of the study was that the researchers did not have information on any over the counter drugs that were taken. However, the only NSAID available in Denmark without prescription is ibuprofen, which is sold only in low dosage (200 mg) and in small packages with a maximum of 20 tablets.
The authors acknowledged that the study was observational, so any conclusion on causality should be made with caution. Gunnar Gislason, study author and professor of cardiology at Copenhagen University Hospital Gentofte in Denmark, said, “I don’t think these drugs should be sold in supermarkets or petrol stations where there is no professional advice on how to use them. Over the counter NSAIDs should only be available at pharmacies, in limited quantities, and in low doses.”
He added, “Do not take more than 1200 mg of ibuprofen per day. Naproxen is probably the safest NSAID, and we can take up to 500 mg a day. Diclofenac is the riskiest NSAID and should be avoided by patients with cardiovascular disease and the general population. Safer drugs are available that have similar painkilling effects so there is no reason to use diclofenac.”
