Efficacy and safety of anticoagulation for atrial fibrillation in patients with cirrhosis: A systematic review and meta-analysis

Chokesuwattanaskul, Ronpichai; Thongprayoon, Charat; Bathini, Tarun; Torres‐Ortiz, Aldo; O'Corragain, O.A.; Watthanasuntorn, Kanramon; Lertjitbanjong, Ploypin; Sharma, Konika; Prechawat, Somchai; Ungprasert, Patompong; Kröner, Paul T.; Wijarnpreecha, Karn; Cheungpasitporn, Wisit

doi:10.1016/j.dld.2018.12.001

Cited by 59 publications

(54 citation statements)

References 38 publications

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“…For this reason, some meta‐analyses investigated the use of DOACs only in patients with chronic liver disease and AF 4‐6 . However, these analyses did not investigate relevant clinical characteristics of patients as the presence of oesophageal varices or advanced Child‐Pugh class.…”

Section: Introductionmentioning

confidence: 99%

Direct oral anticoagulants and advanced liver disease: A systematic review and meta‐analysis

Menichelli

Ronca

Rocco

et al. 2020

Eur J Clin Investigation

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Background Direct oral anticoagulants (DOACs) are recommended for stroke prevention in patients with atrial fibrillation (AF) or for treatment of deep vein thrombosis, although some concerns about safety and efficacy were raised on the use of these drugs in patients with advanced liver disease (ALD). We want to investigate the association of DOACs use with the bleeding and ischaemic risk. Material and Methods We performed a systematic review and metanalysis of clinical studies retrieved from PubMed (via MEDLINE) and Cochrane (CENTRAL) databases addressing the impact of DOACs therapy on bleeding events including intracranial haemorrhage (ICH), gastrointestinal and major bleeding. Secondary end points were all‐cause death, ischaemic stroke/systemic embolism (IS/SE) and recurrence/progression of vein thrombosis (rDVT). Results 12 studies were included in the meta‐analysis: a total of 43 532 patients with ALD or cirrhosis, of whom 27 574 (63.3%) were on treatment with DOACs and 15 958 were in warfarin/low molecular weight heparin. DOACs reduced the incidence of major bleeding by 61% (pooled Hazard Ratio [HR] 0.39, 95% Confidence Interval [CI] 0.21‐0.70), ICH by 52% (HR 0.48, 95% CI 0.40‐0.59), while no difference in the reduction of any and gastrointestinal bleeding were observed. DOACs reduced also rDVT by 82% (HR 0.18, 95%CI 0.06‐0.57), but did not reduce death and IS/SE. No difference was shown according to oesophageal varices and Child Pugh score in the meta‐regression analysis between warfarin/heparin and DOACs performed on each outcome. Conclusions DOACs are associated with a lower incidence of bleeding and may be an attractive therapeutic option in patients with cirrhosis.

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Section: Introductionmentioning

confidence: 99%

Direct oral anticoagulants and advanced liver disease: A systematic review and meta‐analysis

Menichelli

Ronca

Rocco

et al. 2020

Eur J Clin Investigation

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“…However, this cohort, as well as the cohort of patients with prior liver disease, comprised small sample sizes. The results, based on very small numbers of cases, should therefore be interpreted cautiously and in the light of the potential benefit of NOAC therapy in patients with cirrhosis 39 .…”

Section: Strengths and Limitationsmentioning

confidence: 97%

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

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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

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“…Finally, two previously published metanalyses have evaluated the use of warfarin and DOACs in cirrhotic patients including some of the above reported studies. The first including 19,798 cirrhotic patients with AF from seven cohort studies, two of which comparing DOACs vs warfarin [81,83], had two main findings: (a) the use of warfarin was associated with a lower risk of stroke compared with no anticoagulation (HR 0.58) without a significantly increased bleeding risk (HR 1.45), (b) the use of DOACs was associated with a lower risk of bleeding among AF patients with cirrhosis (OR 1.93) [95]. The second, including 447 cirrhotic patients from five studies [77,79,81,82,84] undergoing anticoagulant therapy (DOACs vs warfarin/LMWH) owing to various indications, found that patients treated with DOACs had no significantly increased risk of all-cause bleeding [relative risk (RR) 0.72] and major bleeding (OR 0.46) as compared to those who received traditional anticoagulants [96].…”

Section: Evidence From Real-world Studiesmentioning

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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Efficacy and safety of anticoagulation for atrial fibrillation in patients with cirrhosis: A systematic review and meta-analysis

Cited by 59 publications

References 38 publications

Direct oral anticoagulants and advanced liver disease: A systematic review and meta‐analysis

Direct oral anticoagulants and advanced liver disease: A systematic review and meta‐analysis

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

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

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