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Cardiovascular and gastrointestinal safety of selective cyclooxygenase-2 inhibitors: a case/non-case study

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Abstract

Background Coxibs cardiovascular (CV) safety continues being a current issue after rofecoxib worldwide withdrawal in 2004. Objective To evaluate the cardiovascular and gastrointestinal (GI) risk of coxibs through case/non-case study. Setting The Spanish Pharmacovigilance System for Human Use Drugs (FEDRA) and the Uppsala Monitoring Centre (VigiBase) databases. Method We identified adverse drug reactions (ADRs) cases reported under the MedDRA system organ classes of “cardiac disorders”, “vascular disorders”, “nervous system disorder” and “gastrointestinal disorders”. Disproportionality was considered when the following criteria were met simultaneously: proportional reporting ratio (PRR) ≥ 2, 95% confidence interval lower limit of reporting odds ratio (ROR) > 1, Chi square test (χ2) ≥ 4; and number of ADR reports (n rep.) > 3. Main outcome measure Potential disproportionality between cardiovascular and GI ADRs as reported to FEDRA and VigiBase and the use of coxibs. Results We found association between coxibs and CV-ADRs in FEDRA [PRR 2.11 (95% CI 1.97–2.27); ROR 2.53 (95% CI 2.29–2.89); χ2 367.81; n rep., 561] and VigiBase [PRR 2.67 (95% CI 2.64–2.71); ROR 3.26 (95% CI 3.20–3.31); χ2 23,950.93; n rep., 21,047]; and between coxibs and GI-ADRs in VigiBase [PRR 2.91 (95% CI 2.84–2.97); ROR 3.08 (95% CI 3.01–3.16); χ2 8762.82; n rep. 6954]. No association was found between coxibs and GI-ADRs in FEDRA. Conclusion The association found support a potential coxibs class effect in terms of cardiovascular safety. Classical NSAIDs GI risk may be higher than that for coxibs.

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Authors and Affiliations

  1. Centre for Drug Surveillance (CESME), School of Medicine, Valladolid University, Valladolid, Spain

    Luis Hermenegildo Martin Arias, Rosario Sanz Fadrique & Maria Sainz

  2. Department of Pharmacy, Sagrado Corazón Hospital, Valladolid, Spain

    Antonio Martin Gonzalez

  3. Department of Pharmacology, School of Medicine, Oviedo University, Valladolid, Spain

    Esther Salgueiro

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  1. Luis Hermenegildo Martin Arias
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Correspondence to Antonio Martin Gonzalez.

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Martin Arias, L.H., Martin Gonzalez, A., Sanz Fadrique, R. et al. Cardiovascular and gastrointestinal safety of selective cyclooxygenase-2 inhibitors: a case/non-case study. Int J Clin Pharm 40, 928–935 (2018). https://doi.org/10.1007/s11096-018-0705-x

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