Efficacy and safety of direct oral anticoagulants versus vitamin K antagonist for portal vein thrombosis in cirrhosis: A systematic review and meta-analysis.

Portal vein thrombosis (PVT) is associated with a higher risk of liver-related complications. Recent guidelines recommend direct-acting anticoagulants (DOAC) in patients with cirrhosis and non-tumoral PVT. However, data on the efficacy and safety of DOAC in these patients remain limited. We aim to investigate the efficacy and safety of DOAC compared to vitamin K antagonists (VKA) to treat non-tumoral PVT in patients with cirrhosis. We performed a systematic search of six electronic databases using MeSH term and free text. We selected all studies comparing the use of DOACs with vitamin K antagonist to treat PVT in cirrhosis. The primary outcome was PVT recanalization. Secondary outcomes were and PVT progression, major bleeding, variceal bleeding and death. From 944 citations, we included 552 subjects from a total of 11 studies (10 observational and 1 randomized trial) that fulfilled the inclusion criteria. We found that DOAC were associated with a higher pooled rate of PVT recanalization (RR = 1.67, 95%CI: 1.02, 2.74, I2 = 79%) and lower pooled risk of PVT progression (RR = 0.14, 95%CI: 0.03-0.57, I2 = 0%). The pooled risk of major bleeding (RR = 0.29, 95%CI: 0.08-1.01, I2 = 0%), variceal bleeding (RR = 1.29, 95%CI: 0.64-2.59, I2 = 0%) and death (RR = 0.31, 95%CI: 0.01-9.578, I2 = 80%) was similar between DOAC and VKA. For the treatment of PVT in patients with cirrhosis, the bleeding risk was comparable between DOAC and VKA. However, DOAC were associated with a higher pooled rate of PVT recanalization. Dedicated randomized studies are needed to confirm these findings.

Koh JH ，Liew ZH ，Ng GK ，Liu HT ，Tam YC ，De Gottardi A ，Wong YJ ... -  《-》

Harmful and Beneficial Effects of Anticoagulants in Patients With Cirrhosis and Portal Vein Thrombosis.

Vitamin K antagonists (VKAs) promote recanalization of portal vein thrombosis (PVT) in patients with cirrhosis. However, the benefit of PVT recanalization might be offset by major and minor bleeding associated with use of anticoagulants. We evaluated harmful and beneficial effects of VKA in patients with PVT and cirrhosis. We performed a retrospective study of 63 consecutive patients with cirrhosis given anticoagulants for the first detection of non-neoplastic PVT from 2003 to 2015 in Italy. We collected data on bleeding events in these patients and compared them with those from patients without cirrhosis with venous thromboembolism (VTE) (n = 160) for up to 4 years. Time in the therapeutic range, based on the international normalized ratio, was used to determine the quality of anticoagulation. We also collected data from 139 patients with cirrhosis who did not receive VKAs (controls), to analyze portal hypertension-related events. We performed survival analyses to determine the effects of VKA in patients with PVT vs controls. The group with VTE and the group with PVT were comparable in age, sex, and time in the therapeutic range, but patients with VTE received VKAs for a longer time period (31.1 ± 16.9 mo vs 23.3 ± 16.2 mo; P = .002). The incidence of major or minor bleeding was higher in patients with PVT than patients with VTE (major, 24% vs 7%; P = .012; minor, 29% vs 19%; P = .024). Patients with PVT had a higher rate of major bleeding from the upper-gastrointestinal tract than patients with VTE (P = .019), but there were no significant differences in other types of major bleeding (P = .376). Patients with PVT and controls had the same rate of upper-gastrointestinal bleeding. Complete recanalization in patients with PVT receiving VKA (n = 31) was independently associated with increased portal hypertension-related event-free and transplantation-free survival times. In a retrospective analysis of 63 patients with cirrhosis given anticoagulants for PVT, we found VKA use to increase risk of minor bleeding, compared with patients without cirrhosis given VKA. However, this risk is offset by the ability of VKA to increase portal hypertension-related, event-free, and transplantation-free survival of patients with PVT recanalization. Portal hypertension, rather than anticoagulants, could account for the difference in risk of major bleeding between patients with PVT vs patients with VTE.

La Mura V ，Braham S ，Tosetti G ，Branchi F ，Bitto N ，Moia M ，Fracanzani AL ，Colombo M ，Tripodi A ，Primignani M ... -  《-》

Effects of Anticoagulants in Patients With Cirrhosis and Portal Vein Thrombosis: A Systematic Review and Meta-analysis.

Liver cirrhosis is complicated by bleeding from portal hypertension but also by portal vein thrombosis (PVT). PVT occurs in approximately 20% to 50% of patients with cirrhosis, and is a warning sign for poor outcome. It is a challenge to treat patients with cirrhosis using anticoagulants, because of the perception that the coexistent coagulopathy could promote bleeding. We performed a systematic review and meta-analysis to determine the effects of anticoagulant therapy in patients with cirrhosis and PVT. We searched the PubMed, ISI Web of Science, SCOPUS, and Cochrane databases through February 14, 2017, for studies that assessed the effect of anticoagulant therapy vs no treatment in patients with cirrhosis and PVT. We performed a meta-analysis to estimate the effect of anticoagulant treatment vs no therapy on recanalization and progression of PVT in patients with cirrhosis. We also assessed variceal and nonvariceal bleeding. We analyzed data from 8 studies, comprising 353 patients, that assessed the effects of anticoagulant therapy (low-weight heparin or warfarin vs no therapy) in patients with cirrhosis and PVT; these studies reported rates of complete and partial recanalization. A significantly higher proportion of patients treated with anticoagulants underwent PVT recanalization than patients who did not receive anticoagulants (71% vs 42%, respectively; P < .0001). From 6 studies (comprising 217 patients), 53% of patients treated with anticoagulants vs 33% of patients who did not receive anticoagulants had complete PVT recanalization (P = .002). From 6 studies (comprising 225 patients), PVT progressed in 9% of patients treated with anticoagulants vs 33% of patients who did not receive these drugs (P < .0001). Six studies (257 patients) reported rates of any bleeding; there was no difference in the proportions of patients with major or minor bleeding between groups that did vs did not receive anticoagulants (11% for both groups). Four studies (comprising 158 patients) reported rates of spontaneous variceal bleeding, which occurred in a significantly lower proportion of patients who received anticoagulants vs those who did not (P = .04). Based on a systematic review and meta-analysis, patients with cirrhosis and PVT who receive anticoagulant therapy have increased recanalization and reduced progression of thrombosis, compared with patients who do not receive anticoagulants, with no excess of major and minor bleedings and less incidence of variceal bleeding.

Loffredo L ，Pastori D ，Farcomeni A ，Violi F ... -  《-》

Anticoagulation Favors Thrombus Recanalization and Survival in Patients With Liver Cirrhosis and Portal Vein Thrombosis: Results of a Meta-Analysis.

Wang L ，Guo X ，Xu X ，De Stefano V ，Plessier A ，Noronha Ferreira C ，Qi X ... -  《-》

Comparing the efficacy and safety of direct oral anticoagulants with vitamin K antagonist in cerebral venous thrombosis.

Lee GKH ，Chen VH ，Tan CH ，Leow AST ，Kong WY ，Sia CH ，Chew NWS ，Tu TM ，Chan BPL ，Yeo LLL ，Sharma VK ，Tan BYQ ... -  《-》