Cardiovascular safety of non-steroidal anti-inflammatory drugs revisited

ABSTRACT

Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used to treat inflammatory pain for decades. More recently, newer NSAIDs were developed to target the inducible isoform of cyclooxygenase (COX), COX-2, with the aim of reducing gastrointestinal toxicity. While the COX-2 selective inhibitors were effective in reducing pain and gastrointestinal harm, they soon were associated with an increased risk of adverse cardiovascular events. Initially, the view emerged that selective inhibition of COX-2, and sparing of COX-1, was responsible for the increased cardiovascular harm observed. However, as more data from different human populations has become available this view has begun to be challenged. This review examines the current understanding of the role of prostaglandins and COX-1 and COX-2, particularly in platelets, the vasculature, and the kidney together with an overview of the cardiovascular and renal safety of both traditional NSAIDs and COX-2 selective inhibitors. Available data from active comparator randomized controlled trials, including the data from the PRECISION trial investigating the long term cardiovascular safety of patients exclusively with elevated baseline cardiovascular risk, are presented. The data, when considered holistically, support the idea that all NSAIDs carry some level of cardiovascular risk, be they traditional NSAIDs or COX-2 selective agents. There is also some evidence of heterogeneity of effect with NSAIDs particularly in relation to effects on blood pressure, with no clear demarcation based on the degree of COX-2 selectivity.

KEYWORDS:

• Non-steroidal anti-inflammatory drugs
• cardiovascular
• renal
• osteoarthritis
• COX-2
• COX-2 selective inhibitors

Declaration of interest

C Walker is an employee of Pfizer and holds stock options with Pfizer. LM Biasucci is a recipient of a research grant from Astra-Zeneca and in the last 3 years has received fees for speeches from Pfizer, Bayer and Siemens. Medical writing support was provided by Joshua Fink, PhD, of Engage Scientific Solutions, and funded by Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This manuscript was sponsored by Pfizer.