Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in the United States and the most widely prescribed agents in the world.1 A recent survey found that 12.8% of Americans (an estimated 29.4 million individuals) reported taking NSAIDs regularly – a 41% increase since 2005.2

NSAIDs are associated with many worrisome side effects, the most common being the risk of gastrointestinal (GI) events, with an increase of risk of serious GI complications of between 2.5- and 5-fold, as compared with risk in individuals not taking NSAIDs.1

NSAIDs also carry the risk of cardiovascular disease (CVD). In 2004 and 2005, the US Food and Drug Administration (FDA) recommended that two NSAIDs (the cyclooxygenase [COX]-2 inhibitors rofecoxib and valdecoxib respectively) be removed from the market because of increased cardiovascular events. Individuals with existing CVD may be at particular risk for cardiovascular events if they use NSAIDs. A recent article reviews the safety of NSAIDs in general, and particularly in this population.3

NSAIDs’ Mechanism of Action

There are several mechanisms through which NSAIDs increase cardiovascular risk, including alterations in thromboxane and prostacyclin balance, attenuation of the beneficial effects of cardiovascular medications (eg, aspirin and inhibitors of the renin-angiotensin-aldosterone [RAS] system), and increased sodium and fluid retention.3,4 In particular, the COX-2 inhibitors inhibit the potential beneficial effects of vasodilation and platelet inhibition mediated by endogenous prostacyclin.4