Mortality and oral anticoagulants in the Food and Drug Administration Adverse Event Reporting System

Serebruany, Victor L.; Cherepanov, Vasily; Fortmann, Seth D.; Kim, Moo Hyun

doi:10.1136/openhrt-2017-000629

Cited by 9 publications

(12 citation statements)

References 12 publications

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“…Our analysis of over 40 000 oral anticoagulant–related adverse event cases reported to the FDA found rivaroxaban had a numerically higher rate of the included adverse events, and a significantly higher proportional reporting ratio for breakthrough venous thromboembolism. Our findings are parallel to prior work using FAERS to assess DOAC safety some of which found disproportionate safety reports with rivaroxaban . Our findings also parallel multiple large observational studies that comparatively evaluate DOACs, several of which have found increased thromboembolic events and bleeding with rivaroxaban as compared with other oral anticoagulants .…”

Section: Discussionsupporting

confidence: 84%

A comparative analysis of the safety profile of direct oral anticoagulants using the FDA adverse event reporting system

DeLoughery

Shatzel

2019

European J of Haematology

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Introduction: Direct oral anticoagulants (DOACs) are being increasingly used. However, unlike warfarin, less is known regarding their long-term side effects. To better evaluate the rates of DOAC-related adverse events (AEs) on a population level we examined AEs reported to the FDA for three commonly used DOACs and warfarin. Methods: We evaluated the FDA Adverse Event Reporting System (FAERS) database, which compiles reported drug-related AEs from 1969 onwards. The safety profiles of the included drugs were assessed by comparing AEs per outpatient prescription and with proportional reporting ratios (PRR). Results: Rivaroxaban had the highest proportion of reported AEs. Most notably the rate for breakthrough venous thromboembolism (VTE) was higher than other DOACs. Dabigatran had the highest reported rated of ischemic stroke. When the DOAC data was analyzed using PRR, reported rates of VTE were again higher with rivaroxaban while dabigatran again showed slightlyhigher than expected rates of ischemic stroke. Apixaban did not show higher than expected rates in any category. Conclusion: Our analysis found rates of reported breakthrough VTE were significantly higher with rivaroxaban, while apixaban had no higher than expected rates of any studied AEs.

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Section: Discussionsupporting

confidence: 84%

A comparative analysis of the safety profile of direct oral anticoagulants using the FDA adverse event reporting system

DeLoughery

Shatzel

2019

European J of Haematology

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“…However, the reduction in mortality risk as a secondary endpoint in clinical trials was not significant for NOACs [7][8][9], with the exception of edoxaban [14]. While some observational studies suggest a reduced risk of all-cause mortality among NOAC users, as compared to VKAs [15][16][17][18][19][20][21][22], the evidence is conflicting. Importantly, many observational studies use an ever versus never exposure definition that does not permit switching between medications.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, in many of these studies, they were unable to statistically adjust for lifestyle factors that may influence mortality, such as body mass index and smoking status. Finally, these studies did not exclude prior aspirin use in AF [15][16][17][18][19][20][21][22][23][24][25][26]. Although low-dose aspirin has been removed from the treatment guidelines for AF, use is still observed.…”

Section: Introductionmentioning

confidence: 99%

Mortality risk in atrial fibrillation: the role of aspirin, vitamin K and non-vitamin K antagonists

et al. 2019

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Background As an alternative to vitamin K antagonist and low-dose aspirin (< 325 mg), non-vitamin K oral anticoagulants are available for the prevention of stroke in patients with atrial fibrillation. However, the mortality risk associated with these drugs in daily practice remains unclear. Objective To evaluate the risk of all-cause mortality associated with non-Vitamin K antagonist oral anticoagulants, vitamin K antagonists or aspirin in patients with atrial fibrillation. Setting A cohort study conducted among atrial fibrillation patients using the UK Clinical Practice Research Datalink (March 2008-October 2014). Method New users of vitamin K antagonists, non vitamin K oral anticoagulants, low-dose aspirin, or combination therapy were followed from the date of first prescription to the date of death, as recorded in the UK datalink. Cox proportional hazard models estimated the hazard ratio (HR) of all-cause mortality for users of NOACs, aspirin, or combination use, as compared to vitamin K antagonist. Analyses were adjusted for confounders. Main outcome measure All-cause mortality. Results We identified 31,497 patients. Non vitamin K antocoagulant use (adjusted HR [aHR] = 1.42; 95% Confidence Interval [CI] 1.18-1.71) and aspirin use (aHR = 1.64; 95% CI 1.57-1.77) were both significantly associated with a higher mortality risk than use of vitamin K antagonists. The higher mortality risk for the non vitamin K anticoagulant use was observed in men (aHR = 1.72; 95% CI 1.25-2.36), but not in women (aHR = 1.28; 95% CI 0.92-1.79. Compared to vitamin K antagonists, mortality risk associated with the non vitamin K anticoagulants and aspirin use was significantly increased in patients with higher stroke risk (CHA 2 DS 2-VASc > 2). Conclusion Non vitamin K oral anticoagulants are associated with a higher risk on all-cause mortality, particularly in men and in patients with higher stroke risk.

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“…The Japanese Adverse Drug Event Report (JADER) and the FDA Adverse Event Reporting System (FAERS) include several million spontaneous reports of drug-associated adverse events from healthcare professionals and pharmaceutical companies [6]. In Japan, JADER was established by the Pharmaceuticals and Medical Devices Agency (PMDA) [7].…”

Section: Methodsmentioning

confidence: 99%

Comparison of Hemorrhagic Risk between Prasugrel and Clopidogrel: a Retrospective Study using Adverse Drug Event Reporting Databases

Hagiwara¹,

Fukuta²,

Niimura³

et al. 2020

Int. J. Med. Sci.

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Background: Prasugrel inhibits platelet aggregation more potently and exerts therapeutic action faster than clopidogrel. In the global phase III trial conducted in Western and South American countries that excluded Asian countries, prasugrel reduced ischemic events but increased hemorrhagic risk compared with clopidogrel in patients with acute coronary syndrome scheduled for percutaneous coronary intervention. In the Japanese phase III trial for similar patients, the efficacy of prasugrel compared with clopidogrel was comparable to the global trial, but the safety could not be confirmed because of an insufficient number of patients. Furthermore, given the strict enrollment criteria, the results of these trials may not be applicable to routine clinical practice. Accordingly, we compared the hemorrhagic risk of prasugrel and clopidogrel in real-world settings by analyzing adverse drug event reports in post-marketing stages provided by the Japanese regulatory authorities and the U.S. Food and Drug Administration (FDA). Methods: We analyzed a total of 3,970 reports for prasugrel (n = 518) or clopidogrel (n = 3,452) between 2014 and 2017 in the Japanese Adverse Drug Event Report (JADER) and a total of 91,914 reports for either prasugrel (n = 5,992) or clopidogrel (n = 85,922) between 2009 and 2019 in the FDA Adverse Event Reporting System (FAERS). Results: In JADER and FAERS, prasugrel was more frequently and significantly associated with hemorrhagic event reports than clopidogrel. After adjustment for known confounders including age, sex, and concomitant medications (aspirin, anticoagulants, and proton pump inhibitors), the hemorrhagic risk of prasugrel compared with clopidogrel remained significant (adjusted reporting odds ratios [95% CI] for total, intracranial, and gastrointestinal hemorrhagic events = 2.42 [1.97-2.96], 2.45 [1.85-3.24], and 2.27 [1.73-2.97] in JADER, and 2.21 [2.09-2.34], 1.21 [1.09-1.33], and 1.41 [1.29-1.54] in FAERS). Conclusions:The hemorrhagic risk was found to be greater with prasugrel than clopidogrel in real-world patients, including Japanese patients.

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Mortality and oral anticoagulants in the Food and Drug Administration Adverse Event Reporting System

Cited by 9 publications

References 12 publications

A comparative analysis of the safety profile of direct oral anticoagulants using the FDA adverse event reporting system

A comparative analysis of the safety profile of direct oral anticoagulants using the FDA adverse event reporting system

Mortality risk in atrial fibrillation: the role of aspirin, vitamin K and non-vitamin K antagonists

Comparison of Hemorrhagic Risk between Prasugrel and Clopidogrel: a Retrospective Study using Adverse Drug Event Reporting Databases

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