CARDIOTOXICITY OF NON-STEROID ANTI-INFLAMMATORY DRUGS

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Abstract

Aim. To provide a scientific review on an unfavorable effect of non-steroidal anti-inflammatory drugs (NSAIDs) on cardiovascular outcomes (high blood pressure (BP), myocardial infarction, stroke, heart failure, atrial fibrillation), which can be united by the term of “cardiotoxicity”. Outcomes and methods. To write this review we searched for publications in Russian and international search engines (PubMed, eLibrary, etc.) since 1993. The review is based on an analysis of large clinical and observational studies and meta-analyzes, which is of great importance in the evidence of the data. Results. NSAIDs are widely used drugs in clinical practice. Along with the well-known gastrointestinal side effects of NSAIDs, a large group of adverse effects are cardiovascular events, which were referred to as “cardiotoxicity” in the 2000s. It was shown that cardiotoxicity of NSAIDs can be determined by the degree of selectivity to the action of cyclooxygenase (COX) -2 and has a dose-dependent and course effect for many drugs. According to a number of meta-analyzes and large clinical and observational studies (registers), the use of NSAIDs can lead to an increase in blood pressure (more than 5 mm Hg) and arterial hypertension (from 10 to 29%), and also counteracts the hypotensive effect of antihypertensive drugs ( p-blockers, angiotensin-converting enzyme inhibitors, calcium antagonists). According to large meta-analyzes, NSAIDs increase the risk of myocardial infarction, stroke, decompensated heart failure, atrial fibrillation, and mortality. These risks are showen both for selective COX-2 inhibitors - coxibs (rofecoxib, etoricoxib) and traditional non-selective NSAIDs (diclofenac, ibuprofen, indomethacin). However, celecoxib has an advantage of reducing the risk of cardiovascular outcomes over other NSAIDs. The unfavorable effect of NSAIDs on cardiovascular outcomes increases with doses or frequency of administration and is seen even with short-term use (less than 7 days), and also increases with high cardiovascular risk. Conclusions. The results of this review showes that in clinical practice there is no obvious safe therapeutic window for NSAIDs, that justifies the need for limited use of NSAIDs, especially in patients with established cardiovascular disease.

About the authors

Marina V. Leonova

Interregional Public Organization “Russian Association of Clinical Pharmacologists”

Email: anti23@mail.ru
чл.-кор. РАЕН, д-р мед. наук, проф., член Межрегиональной общественной организации

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