Non–Vitamin K Antagonist Oral Anticoagulants and Risk of Serious Liver Injury

Douros, Antonios; Azoulay, Laurent; Yin, Hui; Suissa, Samy; Renoux, Christel

doi:10.1016/j.jacc.2018.01.009

Cited by 38 publications

(29 citation statements)

References 33 publications

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“…A drawback of this study would be the fact that the patients enrolled in Child-Pugh class A/B had a higher representation than patients enrolled in Child-Pugh class C, which influenced the statistical significance [20]. It is now considered that the status of the liver function does not influence the indication for anticoagulant therapy or dose adjustments, unlike the renal function [21]. Thromboembolic risk is 2.5 times higher in mild or moderate renal dysfunction and 5 times higher in severe renal dysfunction, and the haemorrhagic risk is at least double compared to the general population [22], thus anticoagulant therapy may be frequently needed in chronic kidney disease, a condition that also involves higher bleeding risk.…”

Section: Metabolism and Elimination Of Noac: Renal Function Hepatic Functionmentioning

confidence: 97%

Overview of Non-Vitamin K Oral Anticoagulants

Cîrstea¹

2020

FARMACIA

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Clotting is a highly complex process and its excessive activation can lead to major risk events. Therefore, anticoagulant treatment is one of the mainstays of pharmacology. Vitamin K antagonists were the only oral anticoagulants available for more than half a century. In the early 2000s new possibilities emerged in this field. The direct and selective mechanism by which they inhibit clotting factors along with their rapid onset of action, the diminished intra-and interindividual variability, the short half-life, the fact that routine therapeutic drug monitoring is not necessary, their strong antithrombotic effect were the main supporting arguments put forth for the use of the direct anticoagulants. Taking into account their innovative aspect, health practitioners were reluctant to prescribe these new drugs and invoked their main shortcomings, both medical (e.g.: lack of an antidote, higher bleeding risk when impaired renal function, certain prescribing restrictions etc.) and financial ones. Why should a non-vitamin K oral anticoagulant (NOAC) be used instead of a vitamin K antagonist? Which would be the best option among the NOACs? These are the most important questions that need answers, which can be obtained by studying the pharmacologic profile of these drugs. RezumatCoagularea sanguină este un proces complex, iar activarea excesivă a acestuia poate duce la situații clinice cu riscuri majore. Tratamentul anticoagulant reprezintă așadar un capitol important al farmacologiei. Pentru mai bine de o jumătate de secol, antivitaminele K au fost singurele anticoagulante orale disponibile. Abia începând cu anul 2000 și-au făcut apariția publicații care anunțau debutul unor noi agenți farmacologici din clasa anticoagulantelor orale. Mecanismul lor direct și selectiv de inhibare a factorilor coagulării și debutul rapid al acțiunii farmacologice, variabilitatea intra-și interindividuală mai redusă a efectului, timpul de înjumătățire mai scurt, lipsa necesității de a monitoriza frecvent intensitatea efectului farmacodinamic, acțiunea antitrombotică eficientă au constituit principalele argumente care le-au impus. Așa cum se întâmplă însă cu tot ceea ce este inovativ, profesioniștii din domeniul medical au fost reticenți față de aceste noi medicamente, dezvăluindu-le rapid principalele neajunsuri, de la aspecte medicale (lipsa unui antidot, riscul hemoragic mai ridicat în cazul unei disfuncții renale, unele restricții de utilizare) până la aspecte pecuniare. De ce am utiliza un anticoagulant nou în detrimentul anticoagulantului tradițional? Dintre noile anticoagulante, ce opțiune ar fi de preferat? Acestea reprezintă cele mai importante dintre multele întrebări la care se poate obține un răspuns prin studierea profilului farmacologic al acestor medicamente.

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Section: Metabolism and Elimination Of Noac: Renal Function Hepatic Functionmentioning

confidence: 97%

Overview of Non-Vitamin K Oral Anticoagulants

Cîrstea¹

2020

FARMACIA

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“…Another study on 51,887 patients with AF (including 3778 patients with concomitant liver disease) from a Canadian healthcare insurance database, who were followed for 68,739 person-years, showed no significant difference in the rates of serious DILI (i.e. hospitalization or death) with DOACs versus warfarin, irrespective of baseline liver status [ 114 ].…”

Section: Hepatic Adverse Effects Of Doacsmentioning

confidence: 99%

Direct Oral Anticoagulants in Patients with Liver Disease in the Era of Non-Alcoholic Fatty Liver Disease Global Epidemic: A Narrative Review

Ballestri¹,

Capitelli²,

Fontana³

et al. 2020

Adv Ther

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Atrial fibrillation (AF) and venous thromboembolism (VTE) are highly prevalent and relevant healthcare issues. Direct oral anticoagulants (DOACs) are now the first-choice for anticoagulant treatment of these conditions displaying a better efficacy/safety profile than vitamin-K antagonists, mainly due to significantly reduced risk of major bleeding, especially of intracranial haemorrhage. Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in developed countries showing a continuously growing prevalence. Nonalcoholic steatohepatitis (NASH), its evolutive form, will be the leading cause for liver transplantation by 2020. NAFLD is independently associated with an increased risk of abnormalities of cardiac structure and function, including cardiac rhythm disorders (mainly AF). Moreover, data suggest an increased risk of unprovoked VTE associated with NAFLD/NASH. Therefore, a growing number of patients with chronic liver disease (CLD) will be candidate for anticoagulant therapy in the near future. Cirrhosis of any etiology is characterized by an unstable thrombosis/bleeding haemostatic balance, making anticoagulant therapy particularly challenging in this condition. Given that patients with significant active liver disease and cirrhosis were excluded from all pivotal randomized controlled trials on DOACs, this comprehensive review aims at critically discussing real-world evidence, including the latest population studies, regarding the use of DOACs in patients with CLD/cirrhosis.

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“…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

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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.

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Non–Vitamin K Antagonist Oral Anticoagulants and Risk of Serious Liver Injury

Cited by 38 publications

References 33 publications

Overview of Non-Vitamin K Oral Anticoagulants

Overview of Non-Vitamin K Oral Anticoagulants

Direct Oral Anticoagulants in Patients with Liver Disease in the Era of Non-Alcoholic Fatty Liver Disease Global Epidemic: A Narrative Review

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

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