Evidence Adds to Cardiac Dangers from Ibuprofen, Diclofenac Use

Researchers are warning about the potential heart risks patients have with the use of non-steroidal anti-inflammatory drug (NSAID), many of which are available over-the-counter.

The understanding that NSAIDs are tied to heart problems isn’t a new concept. The US Centers for Disease Control and Prevention (CDC) alerts about potential cardiac issues, however, there’s various problems with avoiding the drugs altogether. They’re already the most commonly used medications across the globe and can be a good alternative to opioids for managing pain, since they are not addictive.

In the new study published in the European Heart Journal, Cardiovascular Pharmacotherapy, the Copenhagen-based team examined the risk of out-of-hospital cardiac arrest associated with NSAIDs in 28,947 Danish patients. The researchers identified patients who had cardiac arrest from 2001 to 2010.

Data on NSAID use were collected since 1995. The NSAIDs included non-selective (ibuprofen, naproxen, and diclofenac) and COX-2 selective inhibitors (rofecoxib and celecoxib). In the United States, ibuprofen and naproxen are available over-the-counter while diclofenac and celecoxib require prescriptions. Before Merck withdrew rofecoxib (Vioxx) from the market in September 2004, the drug was available by prescription. In Denmark (where the study took place), ibuprofen is the only NSAID available over-the-counter, and only small packages of 200 mg dosages.

“Allowing these drugs to be purchased without a prescription, and without any advice or restrictions, sends a message to the public that they must be safe,” Gunnar H. Gislason, MD, PhD, (photo) professor of cardiology of Copenhagen University Hospital Gentofte, said in a news release.

The study was of case-time-control design where patients were both case and control during two different time periods, controlling for comorbidities. The case period was defined as NSAID use during the 30 days before cardiac arrest and the control period was NSAID use during the preceding 30 days without cardiac arrest.

The findings indicated that ibuprofen and diclofenac were the most commonly used (51% and 21.8%, respectively) of all the NSAIDs. Both drugs were associated with a significant increase of out-of-hospital cardiac arrest: ibuprofen (odds ratio (OR): 1.31; 95% confidence interval (CI) 1.14-1.51) and diclofenac (OR: 1.50; 95% CI 1.23-1.82).

The use of naproxen (OR: 1.29; 95% CI 0.77-2.16), rofecoxib (OR: 1.28; 95% CI 0.74-1.70), and celecoxib (OR: 1.13; 95% CI 0.74-1.70), however, were not significantly associated with out-of-hospital cardiac arrest.

The use of any NSAID was linked to a 31% higher risk of cardiac arrest. For ibuprofen and diclofenac specifically, that statistic became 51% and 22%, respectively.

Gislason said that naproxen may be safest NSAID option up to 500 mg per day. He advised that the general population should not take more than 1200 mg of ibuprofen per day. Diclofenac is believed to be the riskiest and the general population, especially patients with cardiovascular disease, should avoid the drug.

“The findings are a stark reminder that NSAIDs are not harmless,” Gislason continued. “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.”

The study, “Non-steroidal anti-inflammatory drug use is associated with increased risk of out-of-hospital cardiac arrest: a nationwide case-time-control study,” was published in Cardiovascular Pharmacotherapy. The news release was provided by the European Society of Cardiology.

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