Study links diclofenac, ibuprofen with increased risk of cardiac arrest

Study results published in the European Heart Journal - Cardiovascular Pharmacotherapy suggest that non-steroidal anti-inflammatory drugs (NSAIDs), particularly diclofenac and ibuprofen, are associated with an increased risk of cardiac arrest. "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," remarked lead author Gunnar Gislason. "Previous studies have shown that NSAIDs are related to increased cardiovascular risk," Gislason noted, adding that the new "findings are a stark reminder that NSAIDs are not harmless." 

Investigators analysed data on 28 947 patients who had suffered an out-of-hospital cardiac arrest in Denmark between 2001 and 2010. Data were collected on all redeemed prescriptions for NSAIDs from Danish pharmacies since 1995, including the non-selective NSAIDs diclofenac, naproxen and ibuprofen, as well as the COX-2 selective inhibitors rofecoxib and celecoxib. Information was not obtained on over-the-counter (OTC) drugs. Among the total study population, 3376 patients were treated with an NSAID up to 30 days before the event, with ibuprofen and diclofenac being the most commonly used. Researchers compared use of NSAIDs during the 30 days before cardiac arrest, to NSAID use during a preceding 30-day period without cardiac arrest, allowing each patient to serve "as both case and control in two different time periods, eliminating the confounding effect of chronic comorbidities." 

Results from the analysis indicated that use of any NSAID was associated with a 31-percent increased risk of cardiac arrest, with diclofenac and ibuprofen tied to higher risk rates of 50 percent and 31 percent, respectively. The authors found that naproxen, celecoxib and rofecoxib were not significantly associated with increased risk of out-of-hospital cardiac arrest, but noted "these groups were characterised by few events." 

Gislason said "NSAIDs should be used with caution and for a valid indication," adding the drugs "should probably be avoided in patients with cardiovascular disease or many cardiovascular risk factors." He also suggested that OTC NSAIDs "should only be available at pharmacies, in limited quantities, and in low doses," and not in places "where there is no professional advice on how to use them." 

However, the Proprietary Association of Great Britain, the trade body representing manufacturers of OTC medicines, argued the study had "several limitations," and insisted that NSAIDs are safe. The group's CEO John Smith said "information about daily dosage was only based on estimates rather than accurate data and didn't account for OTC use," noting that "prescribed NSAIDs would normally contain a higher dosage than those medicines available over-the-counter and would typically be used for longer durations." 

Meanwhile, study findings reported in The BMJ last September suggested that recent use of prescription NSAIDs, including diclofenac and ibuprofen, raised the risk of hospital admission for heart failure by 19 percent versus past use of the pain drugs. In 2015, the FDA issued a safety communication strengthening an existing label warning that NSAIDs increase the chance of a heart attack or stroke. At the time, the agency indicated that the label update would apply to all prescription NSAIDs, and that it would also request updates to OTC non-aspirin NSAID labels.