scholarly journals All-Cause Mortality and Cardiovascular Outcomes With Non-Vitamin K Oral Anticoagulants Versus Warfarin in Patients With Heart Failure in the Food and Drug Administration Adverse Event Reporting System

2019 ◽  
Vol 26 (6) ◽  
pp. e671-e678
Author(s):  
Thomas G. von Lueder ◽  
Dan Atar ◽  
Stefan Agewall ◽  
Jesper K. Jensen ◽  
Ingrid Hopper ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adverse Event ◽  
Vitamin K ◽  
Reporting System ◽  
Oral Anticoagulants ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Event Reporting ◽  
Patients With Heart Failure ◽  
All Cause Mortality

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

2019 ◽  
Vol 10 ◽  
pp. 204209861987673
Author(s):  
Young-Jin Ko ◽  
Seonji Kim ◽  
Kyounghoon Park ◽  
Minsuk Kim ◽  
Bo Ram Yang ◽  
...  
Keyword(s):  
Adverse Event ◽  
Vitamin K ◽  
Major Bleeding ◽  
Reporting System ◽  
Oral Anticoagulants ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Vitamin K Antagonist ◽  
Event Reporting ◽  
System Database

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.

scholarly journals Analysis of the Safety Profile of Commonly Used Procoagulants Using the FDA Adverse Event Reporting System

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4712-4712
Author(s):  
Emma P. Deloughery ◽  
Joseph J. Shatzel
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Vitamin K ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Off Label Use ◽  
Event Reporting ◽  
Off Label ◽  
Events Data

Abstract Introduction: Though less commonly used than their anticoagulant counterparts, procoagulants have an important role in the reversal of anticoagulation. Four-factor prothrombin complex concentrate (4PCC) is now approved by the U.S. Food & Drug Administration (FDA) for the reversal of major bleeding associated with warfarin, and is often used off-label to reverse direct oral anticoagulants. Three-factor concentrate (3PCC) and off-label use of recombinant activated factor VII (rFVIIa) have filled this role in the past. Vitamin K is also used as a common antidote for warfarin-induced coagulopathy. Comparative data evaluating the safety profiles and relative thrombotic risks of the PCCs and rFVIIa is limited. In order to better evaluate their comparative safety we calculated the rate of adverse events reported to the FDA of each procoagulant. Methods: We evaluated the FDA Adverse Event Reporting System (FAERS) database, which compiles drug-related adverse events reported to the FDA from 1969 onwards, to assess the rate of adverse events reported with various procoagulants. Safety profiles were assessed using proportional reporting ratios (PRR) with the total number of reported cases as the denominator. Adverse events data for each drug (vitamin K, rFVIIa, 3PCC, 4PCC) was gathered from FAERS. Both generic and brand names were used to query the database. Adverse events data was filtered by including only events reported by healthcare professionals. Specific adverse events were chosen apriori based on hypothesized potential complications and included hemorrhagic and thrombotic complications. The PRR with 95% confidence interval was generated for each event, with a cut-off of 2 being used to identify associations. Results: As shown in Table 1 and Figure 1, rFVIIa was associated with increased reports of mortality while 4PCC was associated with ischemic stroke, and all but rFVIIa were associated with high INR. 3PCC displayed an increased association with reports of intracranial hemorrhage (ICH), although there was a low rate of reports for 3PCC. Lesser associations were found between rFVIIa and myocardial infarction (MI), 3PCC and deep-vein thrombosis (DVT), and 4PCC and DVT and ICH. In general, vitamin K had the weakest associations among adverse events. Conclusions: Our analysis found that the rate of reports of death and MI were higher with rFVIIa than other procoagulants, while reports of ischemic stroke and intracranial hemorrhage were more common with PCCs. rFVIIa has been associated with cardiovascular before, a finding reiterated by our study. There are notable limitations of this type of analysis, including the reliance on the accurate reporting of adverse events to the FDA, possibility of duplications of reports in the FAERS database, and the importance of not conflating correlation with causation as it relates to these events. The association between rFVIIa and increased death may be due to rFVIIa's history of off-label use in trauma patients and other patient groups at higher risk for mortality. While 4PCC may be the procoagulant of the present, it does not have a perfect safety profile, and further study is needed to better characterize the complications of 4PCC and ensure that it is used in such a way as to not under- or over-treat the condition. Disclosures No relevant conflicts of interest to declare.

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