Mechanisms Involved in the Adverse Cardiovascular Effects of Selective Cyclooxygenase-2 Inhibitors

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  • Leal-Ramos, Oscar Jesus
    • Other Affiliation: Internal Medicine Service, Hospital General Regional 46, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico
  • Arias-Ruiz, Luis Felipe
    • Other Affiliation: Department of Anatomic Pathology, Médica Sur, Mexico City, Mexico
  • Huerta-Velázquez, José Miguel
    • Other Affiliation: Department of Urology, Centro Médico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico
  • Lamoreaux-Aguayo, José Pablo
    • Other Affiliation: Unidad Medica, Hospital Santa María Chapalita, Guadalajara, Jalisco, Mexico
  • Butcher, Dalton
    • School of Medicine, Department of Pathology and Laboratory Medicine
  • López-Cuellar, Asela Berenice
    • Other Affiliation: Cardiovascular Center, Hospital Santa María Chapalita, Guadalajara, Jalisco, Mexico
  • Orozco-Jiménez, Karina Iveth
    • Other Affiliation: Department of Internal Medicine II, Universidad Autónoma de Guadalajara, Zapopan, Jalisco, Mexico
  • Torres-Bugarín, Olivia
    • Other Affiliation: Department of Internal Medicine II, Universidad Autónoma de Guadalajara, Zapopan, Jalisco, Mexico
Abstract
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for managing inflammation, but they are associated with gastrointestinal and renal toxicity upon long-term use. Selective cyclooxygenase-2 (COX-2) inhibitors, or coxibs, were developed to avoid these adverse effects while maintaining anti-inflammatory efficacy. However, accumulating evidence indicates that coxibs may increase the risk of cardiovascular complications. This review explores the pathophysiological mechanisms underlying adverse cardiovascular effects in patients treated with COX-2 inhibitors. These mechanisms include an imbalance between prothrombotic and antithrombotic factors, an altered endocannabinoid metabolism, and downregulation of PPARδ, contributing to thrombosis. Additionally, COX-2 inhibition disrupts renal prostaglandin synthesis, particularly PGE2 and prostacyclins, reduces EP4 receptor expression in macrophages, promotes chemotaxis, and elevates arterial pressure via increased iNOS, ADMA, and L-NMMA activity. At the molecular level, genetic polymorphisms, matrix metalloproteinases, signaling cross-talk, and direct cardiomyocyte injury are implicated. Collectively, these alterations promote a prothrombotic state, fluid retention, enhanced vasoconstriction, impaired vasodilation, myocardial injury, cell death, and cardiac fibrosis. Despite these risks, coxibs are often prescribed without adequate cardiovascular assessment, particularly in patients with pre-existing cardiovascular risk factors. Greater awareness of these mechanisms is essential to optimize the benefit–risk ratio in clinical decision-making involving selective COX-2 inhibitors.
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  • Article
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  • In Copyright
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  • Attribution 4.0 International
Journal title
  • Cardiovascular Medicine
Journal volume
  • 28
Journal issue
  • 1
Page start
  • 5
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  • English
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  • 1664-204X
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  • Multidisciplinary Digital Publishing Institute

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