Triptans and serious adverse vascular events: data mining of the FDA Adverse Event Reporting System database

Cephalalgia. 2014 Jan;34(1):5-13. doi: 10.1177/0333102413499649. Epub 2013 Aug 6.

Abstract

Aim: The aim of this article is to investigate the vascular safety profile of triptans through an analysis of the United States Food and Drug Administration Adverse Event Reporting System (FDA_AERS) database with a special focus on serious and unexpected adverse events.

Methods: A CASE/NON-CASE analysis was performed on the reports entered in the FDA_AERS from 2004 to 2010: CASES were reports with at least one event included in the MedDRA system organ classes 'Cardiac disorder' or 'Vascular disorders', whereas NON-CASES were all the remaining reports. Co-reported cardiovascular drugs were used as a proxy of cardiovascular risk and the adjusted reporting odds ratio (adj.ROR) with 95% confidence intervals (95% CI) was calculated. Disproportionality signals were defined as adj.ROR value >1. Adverse events were considered unexpected if not mentioned on the relevant label.

Results: Among 2,131,688 reports, 7808 concerned triptans. CASES were 2593 among triptans and 665,940 for all other drugs. Unexpected disproportionality signals were found in the following high-level terms of the MedDRA hierarchy: 'Cerebrovascular and spinal necrosis and vascular insufficiency' (103 triptan cases), 'Aneurysms and dissections non-site specific' (15), 'Pregnancy-associated hypertension' (10), 'Reproductive system necrosis and vascular insufficiency' (3).

Discussion: Our analysis revealed three main groups of unexpected associations between triptans and serious vascular events: ischaemic cerebrovascular events, aneurysms and artery dissections, and pregnancy-related vascular events. A case-by-case assessment is needed to confirm or disprove their plausibility and large-scale analytical studies should be planned for risk rate estimation. In the meantime, clinicians should pay special attention to migraine diagnosis and vascular risk assessment before prescribing a triptan, also promptly reporting any unexpected event to pharmacovigilance systems.

Keywords: Triptans; adverse event reporting system; adverse events; data mining; disproportionality; migraine; pharmacovigilance; vascular events.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Adverse Drug Reaction Reporting Systems / statistics & numerical data*
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • Data Mining / methods
  • Databases, Factual / statistics & numerical data
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Drug-Related Side Effects and Adverse Reactions / etiology*
  • Female
  • Humans
  • Incidence
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Pregnancy
  • Risk Factors
  • Tryptamines / adverse effects*
  • United States / epidemiology
  • United States Food and Drug Administration
  • Vascular Diseases / chemically induced*
  • Vascular Diseases / epidemiology*
  • Young Adult

Substances

  • Tryptamines