NSAID use associated with increased cardiovascular death

An important study recently published in the journal Circulation: Cardiovascular Quality and Outcomes alerts us to a serious hazard associated with non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (Voltaren®), rofecoxib (Vioxx®, now withdrawn), and even ibuprofen to a lesser degree. The authors state:

"Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals."

They analyzed data for 1,028,437 individuals drawn from the entire Danish population by the appropriate selection criteria. By crunching 8 years' worth of numbers they found:

"Use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with an increased risk of cardiovascular death. There was a trend for increased risk of fatal or nonfatal stroke associated with ibuprofen treatment, but naproxen was not associated with increased cardiovascular risk."

The risk was almost doubled for Voltaren and Vioxx. For ibuprofen the risk for stroke was increased by about 30%. Of special note is that the average duration of treatment with these medications was only 14 days. The authors sum up their results:

"In the present nationwide study of healthy individuals, we found that most NSAIDs are associated with increased cardiovascular mortality and morbidity. In particular, the use of the nonselective NSAID diclofenac and the selective COX-2 inhibitor rofecoxib was associated with a similarly increased risk of cardiovascular mortality and morbidity among healthy individuals. Our results suggest that naproxen could be a safer alternative when NSAID treatment is required."

In other words, ibuprofen is not innocent, but Voltaren is as bad as Vioxx. These risks make sense if we consider that NSAIDs also increase intestinal permeability, an aggravating factor for autoimmunity, and recall the autoimmune aspect of cardiovascular disease. They further exhort doctors and public health officials with a stern warning:

"Diclofenac is widely used in the general population worldwide, and it is also accessible as over-the-counter medication in various countries. Our study suggests that this pharmaceutical strategy represents a major public health issue, potentially exposing a substantial number of individuals to risk of cardiovascular adverse events. Physicians initiating NSAID treatment should always make an individual assessment of cardiovascular risk and carefully consider the balance between benefit and risk before starting treatment with any NSAID."