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International Journal of Clinical Pharmacy

, Volume 40, Issue 4, pp 928–935 | Cite as

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

  • Luis Hermenegildo Martin Arias
  • Antonio Martin GonzalezEmail author
  • Rosario Sanz Fadrique
  • Esther Salgueiro
  • Maria Sainz
Research Article

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.

Keywords

Cardiovascular disease Cyclooxygenase 2 inhibitors Epidemiologic study Gastrointestinal disease Non steroidal anti inflammatory agents 

Notes

Funding

No funding was received for preparation of the manuscript.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Supplementary material

11096_2018_705_MOESM1_ESM.docx (75 kb)
Supplementary material 1 (DOCX 74 kb)

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Centre for Drug Surveillance (CESME), School of MedicineValladolid UniversityValladolidSpain
  2. 2.Department of PharmacySagrado Corazón HospitalValladolidSpain
  3. 3.Department of Pharmacology, School of MedicineOviedo UniversityValladolidSpain

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