Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs with analgesic, anti-inflammatory, and antipyretic activity. Their effect is achieved by the reduction in synthesis of prostanoids. Inhibition of prostanoids is responsible for a substantial risk of adverse effects. The risk of side effects affecting the gastrointestinal tract and kidneys has long been known. The possibilities of blood pressure elevation and the development of congestive heart failure are also widely recognized. Increased incidence of acute myocardial infarction in clinical trials with rofecoxib drew attention to the potential cardiotoxicity of selective cyclooxygenase-2 inhibitors, and similarly, concerns have been raised regarding the cardiovascular safety of non-selective NSAIDs. The safety of NSAIDs with regards to cardiovascular events has been studied in recent years in a large number of retrospective and prospective clinical studies and meta-analyses. The results indicate that cardiotoxicity is a class effect, but the magnitude of the risk is widely variable between individual NSAID drugs. This article aims to summarize the available data on the risk of adverse cardiovascular events with NSAIDs, the clinical impact of these events and possible underlying mechanisms.
Highlights
BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) have numerous serious, potentially lifethreatening adverse drug reactions (ADR), yet they belong to the most widely prescribed/used medicines worldwide [1]
The results of both interventional and observational studies point towards the increased CV risk being a class effect of NSAIDs
The level of risk displays a large variability between individual drugs in the group and seems to be affected by the baseline cardiovascular risk of patients, CV ADRs can develop even in individuals without a pre-existing CV condition
Summary
Nonsteroidal anti-inflammatory drugs (NSAIDs) have numerous serious, potentially lifethreatening adverse drug reactions (ADR), yet they belong to the most widely prescribed/used medicines worldwide [1]. The Vioxx Gastrointestinal Outcomes Research (VIGOR) study unexpectedly discovered an increased incidence of myocardial infarction (MI) in patients treated with the selective cyclooxygenase-2 inhibitor rofecoxib, compared to naproxen [6]. After the discovery of increased risk of thrombotic events with COX-2 inhibitors, scientists focused their efforts on ruling out or confirming similar ADRs of non-selective NSAIDs. in recent years, the cardiovascular safety of NSAIDs has been addressed in many clinical trials and meta-analyses. The increased risk of thrombotic events mediated by non-selective NSAIDs and selective COX-2 inhibitors has been shown by large-scale epidemiological studies. Et al [48] compared in their cohort study the risk of hospitalization for congestive heart failure in patients treated with coxibs, non-selective NSAIDs and controls. The perception of risk of CHF exacerbation caused by NSAIDs seems to be higher in the medical community than the perception of risk of other CV adverse effects, since according to new data, patients with CHF are less likely to get an NSAID prescribed patients with other forms of CV disease [49]
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