Cardiovascular and Gastrointestinal Safety of Non-Steroidal Anti-Inflammatory Drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) constitute a cornerstone of pain management and anti-inflammatory therapy worldwide. By inhibiting cyclo-oxygenase (COX) enzymes, NSAIDs reduce prostanoid synthesis, alleviating pain and inflammation but also compromising gastrointestinal mucosal defence and modulating vascular homeostasis. Non-selective NSAIDs block both COX-1 and COX-2 isoforms, risking mucosal injury throughout the gastrointestinal tract, while COX-2-selective agents were developed to spare COX-1-mediated gastroprotection. However, the latter have been linked to prothrombotic shifts in the balance of prostacyclin and thromboxane, elevating the risk of myocardial infarction and stroke. Clinical outcomes vary across compounds and dosages: naproxen and low-dose ibuprofen generally exhibit the most favourable cardiovascular profiles but still require judicious use in patients with existing vascular disease. Concomitant gastroprotective measures, such as proton pump inhibitors or misoprostol, have mitigated upper gastrointestinal complications, yet lower gastrointestinal ulcers and bleeding remain problematic. The dual threats to the cardiovascular and gastrointestinal systems demand individualised risk–benefit assessments, especially in older adults, patients with comorbidities and those on concurrent anticoagulant or antiplatelet therapies. Recent advances in understanding prostanoid biology and real-world prescribing patterns underline the need for ongoing vigilance and refined therapeutic strategies to optimise safety across diverse patient populations.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Cardiovascular and Gastrointestinal Safety of Non-Steroidal Anti-Inflammatory Drugs publication trend

The graph below shows the total number of articles in cardiovascular and gastrointestinal safety of non-steroidal anti-inflammatory drugs across all publications each year (not limited to Nature Index journals).

Technical terms

Non-steroidal anti-inflammatory drug (NSAID): A class of analgesic and anti-inflammatory agents that inhibit cyclo-oxygenase enzymes to reduce prostanoid synthesis.

Cyclo-oxygenase (COX) isoforms: Enzymes COX-1, involved in physiological homeostasis such as gastric mucosal protection and platelet function, and COX-2, induced during inflammation to generate prostanoids.

Prostacyclin: A vasodilatory and anti-platelet prostanoid produced via COX pathways that counteracts thromboxane-mediated vasoconstriction and platelet aggregation.

Gastroprotection: Strategies, including proton pump inhibitors or mucosal prostaglandin analogues, aimed at preventing NSAID-induced damage to the upper and lower gastrointestinal mucosa.

Quality-adjusted life year (QALY): A composite measure that integrates both the quantity and quality of life lived, used to assess the value of medical interventions.

References

1. Estimating the economic effect of harm associated with high risk prescribing of oral non-steroidal anti-inflammatory drugs in England: population based cohort and economic modelling study. The BMJ (2024).
2. Widening the Prostacyclin Paradigm: Tissue Fibroblasts Are a Critical Site of Production and Antithrombotic Protection. Arteriosclerosis Thrombosis and Vascular Biology (2023).
3. A Comprehensive Review of Non-Steroidal Anti-Inflammatory Drug Use in The Elderly. Aging and Disease (2018).