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. 2019 Sep 24:10:2042098619876737.
doi: 10.1177/2042098619876737. eCollection 2019.

Comparison of bleeding risks among non-vitamin K antagonist oral anticoagulants using the Korea adverse event reporting system database

Young-Jin Ko  1 , Seonji Kim  1 , Kyounghoon Park  1 , Minsuk Kim  2 , Bo Ram Yang  3 , Joongyub Lee  4 , Mi-Sook Kim  3 , Byung-Joo Park  5
Affiliations

Comparison of bleeding risks among non-vitamin K antagonist oral anticoagulants using the Korea adverse event reporting system database

Young-Jin Ko et al. Ther Adv Drug Saf. .

Abstract

Background: In order to ensure safer use of non-vitamin K antagonist oral anticoagulants (NOACs), continuously detecting unexpected adverse drug reactions (ADRs) after market approval is necessary.

Methods: We performed disproportionality analysis to evaluate association between ADRs and NOACs including apixaban, dabigatran, and rivaroxaban using data from the Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System database (KIDS-KD) between 2012 and 2016. There was no significant signal other than bleeding when considering quantity, signal strength, seriousness, and causality. In order to evaluate the NOAC reports about bleeding, we selected 62 WHO-ART diagnostic codes associated with bleeding. Among the 26 codes that referred to major bleeding, 18 codes referred to gastrointestinal bleeding and 8 were referred to intracranial bleeding. We evaluated the significance of the signals using reporting odds ratios (RORs) adjusted for age and sex.

Results: Treatments with apixaban, dabigatran, and rivaroxaban were associated with 1989, 1668, and 2960 adverse events, respectively. Any type of bleeding with apixaban, dabigatran, rivaroxaban, and warfarin was reported in 174 (8.8%), 209 (12.5%), 523 (17.8%), and 620 (9.5%) events, respectively. For any bleeding, adjusted RORs of apixaban, dabigatran, and rivaroxaban were 0.99 [95% confidence interval (CI): 0.83-1.17], 1.47 (95% CI: 1.25-1.75), and 2.48 (95% CI: 2.16-2.84), respectively. With respect to major bleeding, the adjusted RORs of apixaban, dabigatran, and rivaroxaban were 1.08 (95% CI: 0.82-1.41), 1.46 (95% CI: 1.10-1.90), and 1.82 (95% CI: 1.43-2.32), respectively.

Conclusion: Rivaroxaban might have stronger association with bleeding than apixaban and dabigatran.

Keywords: adverse events; bleeding; non-vitamin K antagonist oral anticoagulants; oral anticoagulants.

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Conflict of interest statement

Conflict of interest statement: The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
Flow chart of signal detection and prioritization in KIDS-KD 2012–2016. AE, adverse event; KIDS-KD, Korea Institute of Drug Safety and Risk Management (KIDS)-Korea Adverse Event Reporting System (KAERS) database.
Figure 2.
Figure 2.
aRORs according to type of bleeding in apixaban, dabigatran, rivaroxaban, and warfarin in KIDS-KD 2012–2016. Adjusted for age and gender; horizontal bars represent 95% CIs. ADR, adverse drug reaction; aROR, adjusted reporting odds ratio; CI, confidence interval; GI, gastrointestinal; KIDS-KD, Korea Institute of Drug Safety and Risk Management (KIDS)-Korea Adverse Event Reporting System (KAERS) database.
Figure 3.
Figure 3.
Sequential analyses of aROR of any bleeding in apixaban, dabigatran, rivaroxaban, and warfarin in KIDS-KD 2012–2016. Adjusted for age and gender; vertical bars represent 95% Cis. CIs, confidence intervals; KIDS-KD, Korea Institute of Drug Safety and Risk Management (KIDS)-Korea Adverse Event Reporting System (KAERS) database; ROR, reporting odds ratios.
Figure 4.
Figure 4.
Sequential analyses of aROR of GI bleeding in apixaban, dabigatran, rivaroxaban, and warfarin in KIDS-KD 2012–2016. Adjusted for age and gender; Vertical bars represent 95% CIs. aROR, adjusted reporting odds ratio; CI, confidence interval; GI, gastrointestinal; KIDS-KD, Korea Institute of Drug Safety and Risk Management (KIDS)-Korea Adverse Event Reporting System (KAERS) database.
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References

    1. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22: 983–988. - PubMed
    1. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014; 383: 955–962. - PubMed
    1. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130: e199–e267. - PMC - PubMed
    1. Camm AJ, Lip GY, De Caterina R, et al. 2012 focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012; 33: 2719–2747. - PubMed
    1. Ko YJ, Kim S, Park K, et al. Impact of the health insurance coverage policy on oral anticoagulant prescription among patients with atrial fibrillation in Korea from 2014 to 2016. J Korean Med Sci 2018; 33: e163. - PMC - PubMed

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