‘A major safety concern’: World’s most common NSAID doubles CVD risk

Research out of Denmark suggests diclofenac, the world’s most commonly consumed non-steroidal anti-inflammatory drug (NSAID), poses a major threat to heart health—more so than paracetamol or run-of-the-mill NSAIDs like ibuprofen and naproxen.

The research, led by Morten Schmidt, MD, PhD, of Aarhus University Hospital in Aarhus, Denmark, took the form of 252 nationwide cohort studies, each designed as a clinical trial that would test the efficacy of diclofenac against other painkillers or none at all.

“The cardiovascular risks of NSAIDs remain a major safety concern after rofecoxib’s thromboembolic properties were revealed,” Schmidt and co-authors wrote in the BMJ, where they published their findings this week. “Diclofenac is a traditional NSAID with COX 2 selectivity similar to COX 2 inhibitors, but its cardiovascular risks compared with those of other traditional NSAIDs have never been examined in a randomized controlled trial.”

The authors’ series of studies enrolled 1,370,832 diclofenac initiators, 3,878,454 ibuprofen initiators, 291,490 naproxen initiators and 764,781 paracetamol initiators. Participants all had a low baseline risk for CVD and were monitored for adverse outcomes at the 30-day mark.

Schmidt et al. said that though diclofenac remains the most frequently used NSAID in low-, middle- and high-income countries, its users saw a 50 percent increased adverse event rate when compared to patients who didn’t take the drug. Risk was increased by 20 percent compared with paracetamol or ibuprofen users and 30 percent compared with those who took naproxen.

According to the study, the event rate for diclofenac initiators increased for every aspect of the combined endpoint, including myocardial infarction, stroke, heart failure, ischemic stroke and cardiac death.

“Although the relative risk of major adverse cardiovascular events was highest in individuals with low or moderate baseline risk, the absolute risk was highest in individuals with high baseline risk,” Schmidt and colleagues wrote. “Diclofenac initiation also increased the risk of upper gastrointestinal bleeding at 30 days.”

The authors said treatment of pain and risk management with NSAIDs can be justified, especially when patients are looking to improve their quality of life. But when it comes to diclofenac, they said, there’s little justification.

“It is time to acknowledge the potential health risk of diclofenac and to reduce its use,” they wrote. “Diclofenac should not be available over-the-counter, and, when prescribed, should be accompanied by an appropriate front package warning about its potential risks.”