NSAIDs are the most widely prescribed class of medications worldwide.¹ NSAIDs have an anti-inflammatory effect due to COX-2 inhibition and decrease the release of gastroprotective prostaglandins due to its COX-1 effect, which leads to gastric ulcers. COX-2 inhibitors were developed in order to have an anti-inflammatory effect, but to decrease the effect on gastrointestinal side effects. In 2004, rofecoxib was withdrawn from the market due to cardiovascular adverse effects.² The FDA then mandated a large CV safety trial of the remaining COX-2 inhibitor, celecoxib. The trial showed that celecoxib does not present a greater CV safety risk than the traditional NSAIDs, naproxen and ibuprofen. The trial also confirmed, as expected, that celecoxib has fewer GI side effects. It is important to recognize that this trial compared celecoxib to NSAIDs and showed no difference in CV safety, but did not compare either to a placebo group. In July 2015, the FDA issued an update of its 2005 boxed warning on CV safety of NSAIDs stating, “The US Food and Drug Administration (FDA) is strengthening an existing label warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) increase the chance of a heart attack or stroke…. The risk of heart attack or stroke can occur as early as the first weeks of using an NSAID. The risk may increase with longer use of the NSAID.”² —Neil Skolnik, MD

1. Food and Drug Administration. FDA public health advisory: safety of Vioxx. September 30, 2004. http://www.fda.gov/Drugs/Drug Safety/Postmarket Drug SafetyInformation for Patients and Providers/ucm106274.htm. Accessed November 28, 2016.
2. FDA Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. http://www.fda.gov/Drugs/DrugSafety/ucm451800.htm. Accessed November 28, 2016.