Liver injury with direct-acting anticoagulants: has the fog cleared?

Raschi, Emanuel; Ponti, Fabrizio De

doi:10.1136/heartjnl-2017-311951

Cited by 4 publications

(2 citation statements)

References 4 publications

(4 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both studies defined liver injury as a mix of hospitalised acute and chronic (or unspecified) liver injuries and their estimates were based on small numbers of cases, leading to wide confidence intervals. Results of these observational studies contrasted with those reported from postmarketing pharmacovigilance data 18 , 19 . Furthermore, the risk of liver injury associated with oral anticoagulant (OAC) therapies has never been assessed in patients with concomitant AF and chronic alcoholism, which may concern about 1.9–7.5% of AF patients according to EORP-AF and EHS registry data 20 , 21 .…”

Section: Introductioncontrasting

confidence: 63%

Oral anticoagulants and risk of acute liver injury in patients with nonvalvular atrial fibrillation: a propensity-weighted nationwide cohort study

Maura

Bardou

Billionnet

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Insufficient real-world data on acute liver injury (ALI) risk associated with oral anticoagulants (OACs) exist in patients with nonvalvular atrial fibrillation (NVAF). Using the French national healthcare databases, a propensity-weighted nationwide cohort study was performed in NVAF patients initiating OACs from 2011 to 2016, considering separately those (1) with no prior liver disease (PLD) as main population, (2) with PLD, (3) with a history of chronic alcoholism. A Cox proportional hazards model was used to estimate the hazard ratio with 95% confidence interval (HR [95% CI]) of serious ALI (hospitalised ALI or liver transplantation) during the first year of treatment, for each non-vitamin K antagonist (VKA) oral anticoagulant (NOAC: dabigatran, rivaroxaban, apixaban) versus VKA. In patients with no PLD (N = 434,015), only rivaroxaban new users were at increased risk of serious ALI compared to VKA initiation (adjusted HR: 1.41 [1.05-1.91]). In patients with chronic alcoholism history (N = 13,173), only those initiating dabigatran were at increased risk of serious ALI compared to VKA (2.88 [1.74-4.76]) but an ancillary outcome suggested that differential clinical follow-up between groups might partly explain this association. In conclusion, this study does not suggest an increase of the 1-year risk of ALI in NOAC versus VKA patients with AF. Non-vitamin K antagonist oral anticoagulants (NOACs) use has increased dramatically worldwide over the last 5 years since their introduction for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) 1. The European guidelines now recommend NOACs in preference to vitamin K antagonists (VKAs) in these patients 2. With increasing AF prevalence 3 and, as a more convenient alternative to VKAs 4 , NOAC prescription should continue to increase. Careful monitoring of their safety profile apart from their well-known bleeding adverse events is therefore needed in clinical practice, especially regarding rare adverse events that cannot be observed in randomized clinical trials (RCT) 5. Following market withdrawal of ximelagatran, the first orally available direct thrombin inhibitor, due to reports of severe liver injury 6 , post-marketing data including pharmacovigilance reports have raised concerns about the potential hepatotoxicity of other NOACs 7-9. While all NOACs undergo varying degrees of hepatic metabolism, with much lower hepatic metabolism for dabigatran 10 , cases of drug-induced liver injury, albeit rare and of varying severity, have been reported with dabigatran 11 , rivaroxaban 12 and apixaban 13. Although VKAs have been marketed for decades, acute liver failure has been rarely reported 14,15. Only two published cohort studies based on claims data have compared NOAC and VKA therapies in terms of liver injuries 16,17. Both studies defined liver injury as a mix of hospitalised acute and chronic (or unspecified) liver injuries and their estimates

show abstract

Section: Introductioncontrasting

confidence: 63%

Oral anticoagulants and risk of acute liver injury in patients with nonvalvular atrial fibrillation: a propensity-weighted nationwide cohort study

Maura

Bardou

Billionnet

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…For instance, the analysis by Elashoff et al [16] on pancreatitis reports with incretin-based drugs, apart from methodological flaws and data misinterpretation causing unjustified alarm, was also untimely, considering that observational studies had already been carried out. Conversely, liver injury with direct-acting oral anticoagulants (DOACs) was studies because of limited predictivity of premarketing phases in detecting clinical signals of liver toxicity and previous concern with ximelagatran: the disproportionality signal raised for rivaroxaban in FAERS [116] was tested by the recent US population-based studies, which found lower hospitalization rates for liver injury with DOAC initiators than patients starting warfarin, with rivaroxaban and dabigatran associated with the highest and lowest risk [117,118], although confounders are likely to exist [119,120]. This case underscores the value of performing well-conducted DAs and the importance of directing subsequent analytical research to confirm or refute the drug-related hypothesis.…”

Section: Future Perspectivesmentioning

confidence: 99%

Evolving Roles of Spontaneous Reporting Systems to Assess and Monitor Drug Safety

Raschi¹,

Moretti²,

Salvo³

et al. 2019

Pharmacovigilance

Self Cite

View full text Add to dashboard Cite

This chapter aims to describe current and emerging roles of spontaneous reporting systems (SRSs) for assessing and monitoring drug safety. Moreover, it offers a perspective on the near future, which entails the so-called era of Big Data, keeping in mind both regulator and researcher viewpoints. After a panorama on key data sources and analyses of post-marketing data of adverse drug reactions, a critical appraisal of methodological issues and debated future applications of SRSs will be presented, including the exploitation and challenges in evidence integration (i.e., merging and combining heterogeneous sources of data into a unique indicator of risk) and patient's reporting via social media. Finally, a call for a responsible use of these studies is offered, with a proposal on a set of minimum requirements to assess the quality of disproportionality analysis in terms of study conception, performing and reporting.

show abstract