Cardiovascular risk of NSAIDs: Time to translate knowledge into practice

Citation: Reddy KS, Roy A (2013) Cardiovascular Risk of NSAIDs: Time to Translate Knowledge into Practice. PLoS Med 10(2): e1001389. doi:10.1371/journal.pmed.1001389
Published: February 12, 2013

Linked Research Article

This Perspective discusses the following new study published in PLOS Medicine:

McGettigan P, Henry D (2013) Use of Non-Steroidal Anti-Inflammatory Drugs That Elevate Cardiovascular Risk: An Examination of Sales and Essential Medicines Lists in Low-, Middle-, and High-Income Countries. PLoS Med 10(2): e1001388. doi:10.1371/journal.pmed.1001388

Patricia McGettigan and David Henry find that, although some non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac are known to increase cardiovascular risk, diclofenac is included on 74 countries’ essential medicine lists and was the most commonly used NSAID in the 15 countries they evaluated.

Clinical use of non-steroidal anti-inflammatory drugs (NSAIDs) carries cardiovascular risk, which acquires implications for public health against the backdrop of rising chronic disease rates in low- and middle-income countries (LMICs). New evidence from an international study conducted by Patricia McGettigan and David Henry and published this week in PLOS Medicine [1] sheds light on how emerging evidence about NSAID risk is poorly translated into practice and sales in countries around the world, raising questions about the use and promotion of potentially harmful drugs.

NSAIDs are extensively prescribed for pain management in patients with osteoarthritis and several other painful conditions. The large number of drugs in this group is broadly divided into nonselective cyclo-oxygenase (COX) inhibitors and selective COX inhibitors. This classification is based on the selective inhibition of COX-2 enzyme, which is primarily responsible for the generation of inflammatory mediators. The emergence of selective COX-2 inhibitors in the 1990s was widely welcomed by physicians, as these drugs were expected to reduce the adverse gastrointestinal effects associated with inhibition of COX-1. However, the enthusiasm evaporated when it was discovered that rofecoxib (Vioxx), an early and aggressively marketed molecule of this drug class, increased the risk of serious cardiovascular events [2],[3]. Subsequently, several systematic reviews and meta-analyses showed that other NSAIDs too were associated with adverse cardiovascular events [4]–[6].

The adverse cardiovascular profile of NSAIDs includes risk of atherothrombotic events like myocardial infarction (MI) and stroke, which can be fatal. The increased cardiovascular risk has been observed both in people with a prior high risk of cardiovascular disease and in previously healthy individuals [7], and this risk appears to be dose dependent [8]. What is intriguing, however, is that the increase in cardiovascular risk has been variable with the different molecules. Apart from rofecoxib, diclofenac is the agent most associated with an increased risk of cardiovascular events: a 40%–60% higher relative risk of serious cardiovascular events, compared to non-use of NSAIDs, has been reported [4]–[6],[9]. This is a rate equivalent to or possibly higher than that of rofecoxib, now withdrawn from the market. In contrast, another traditional NSAID, naproxen, has been found to be relatively...

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