You are here

Article Text

Article menu

Download PDFPDF

Arrhythmias and sudden death
Original research article
Mortality and oral anticoagulants in the Food and Drug Administration Adverse Event Reporting System
  1. Victor Serebruany1,2,
  2. Vasily Cherepanov2,
  3. Seth Fortmann2 and
  4. Moo Hyun Kim3
  1. 1 Johns Hopkins University, Baltimore, Maryland, USA
  2. 2 HeartDrug™ Research Laboratories, Towson, Maryland, USA
  3. 3 Dong-A University, Busan, South Korea
  1. Correspondence to Moo Hyun Kim; kimmh{at}dau.ac.kr

Abstract

Objective The comparative crude death rates (CDR) among non-vitamin K antagonist oral anticoagulants (NOACs) are unknown. Further, whether NOACs improve survival when compared with warfarin is also unclear. We compared CDR co-reported for four NOACs combined or separately versus warfarin within the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database.

Methods We selected CDR from the FAERS database linked to four NOACs and warfarin. The primary endpoints were differences in proportional reporting ratios (PRRs), and Chi-Square (χ2)for dabigatran, rivaroxaban, apixaban and edoxaban when compared with warfarin.

Results The FAERS database contains significantly less death reports associated with all NOACs combined (14 917 out of 128 267 reports (11.63%); PRR=1.089; χ2=70.0; p=6.05e−17) than for warfarin (19 493 out of 153 911 reports (12.67%)). The numbers for rivaroxaban (6318 out of 64 512 reports or (9.79%); PRR=1.293; χ2=359.4; p=3.72e−80), apixaban (1693 out of 17 789 reports (9.52%); PRR=1.331; χ2=145.8; p=1.43e−33) and edoxaban (53 out of 755 reports (7.02%); PRR=1.804; χ2=21.18; p=4.18e−06) were favourable as compared with warfarin, while the numbers of fatalities co-reported with dabigatran (6989 out of 46 250 reports (15.11%); PRR=0.838; χ2=185.2; p=3.61e−42) were higher than for warfarin.

Conclusion Overall, based on these CDR, NOACs appear to be associated with a mortality benefit over warfarin. Among NOACs, we observed remarkably similar for factor Xa inhibitors (rivaroxiban, apixaban and edoxaban) but unfavourable signal for the direct thrombin inhibitor (dabigatran). However, these data are clearly not sufficient to change the prescription patterns.

  • Warfarin
  • Dabigatran
  • Rivaroxaban
  • Apixaban
  • Edoxaban
  • Mortality
  • Repository
  • Real World Data

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/openhrt-2017-000629

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • Contributors VS and VC conceived the study and planned the analytical approach. VS, SF and MHK interpreted the results. VS and SF drafted the paper. VC and MHK commented on and edited further drafts. VS produced the final manuscript.

    • Funding This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C1731) and funded by the Ministry of Education to Dr Kim.

    • Competing interests VS received research grants from the dabigatran, rivaroxaban and apixaban manufacturers, lecture fees from the dabigatran, apixaban and edoxaban manufacturers and consultant fees from all four NOACs manufacturers.

    • Provenance and peer review Not commissioned; externally peer reviewed.