not-yet-known not-yet-known not-yet-known unknown Aims: Patients with liver disease, particularly cirrhosis, are often excluded from clinical trials on anticoagulant therapy, therefore, the optimal choice of anticoagulants for this population is still unclear. Methods: We searched the databases of PubMed, the Cochrane Library, Medline, and Embase for relevant studies. Results: In this meta-analysis, we included 19 studies with 51,728 participants. In patients with liver disease, compared with that in the traditional group, the DOAC group showed a significantly lower risk for major bleeding, intracranial bleeding (ICH), gastrointestinal bleeding and composite outcome. We did not observe statistically significant differences between the groups with respect to ischemic stroke/thromboembolism (IS/TE), all-cause mortality. In patients with liver cirrhosis, the DOAC group performed better than the traditional group in terms of major bleeding, gastrointestinal bleeding, ICH, IS/TE + major bleeding and composite outcome. The efficacy and safety of regular-dose and low-dose DOACs showed no difference (P>0.05), whereas the efficacy and safety of apixaban were superior to those of rivaroxaban (P<0.05). Conclusion: The effectiveness of DOACs for anticoagulation treatment in patients with liver disease was not inferior to that of traditional anticoagulation regimens, and the safety of DOACs was better. The results were also applicable to patients with cirrhosis. When selecting among DOACs, apixaban demonstrated superior efficacy and safety compared to rivaroxaban. Furthermore, the clinical benefits observed between regular-dose and low-dose DOACs showed no significant difference.

Aim: As the non-vitamin K antagonist oral anticoagulant (NOAC) most recently approved in China, data pertaining to clinical edoxaban use are still scarce. This study investigated the prevalence of and contemporary trends in edoxaban prescription among Chinese patients as well as factors associated with its inappropriate use in a multi-center registry of patients treated in real-world clinical practice. Methods: This real-world, prospective, multicenter, and non-interventional study included 1005 inpatients treated with edoxaban. According to National Medical Products Administration and European Heart Rhythm Association guidelines, edoxaban therapy was determined to be appropriate or inappropriate in each case. Results: The median patient age was 70.0 years (interquartile range, 61.0–78.0 years), and 46.3% were women. Overall, 456 (45.4%) patients received inappropriate edoxaban therapy, and common issues included an inappropriately low (183, 18.2%) or high (73, 7.3%) dosage, wrong drug selection (109, 10.8%), unreasonable off-label use (49, 4.9%), incorrect administration timing (16, 1.6%), and contraindication due to other medications (27, 2.7%). Several factors (e.g., age, weight, kidney function, anemia, and bleeding history) were associated with an increased risk of inappropriate edoxaban therapy, whereas factors associated with cardiovascular specialties (e.g., hospitalized in cardiovascular department and dronedarone or amiodarone use) decreased this risk. Conclusion: In this real-world study, 45.4% of patients received an inappropriate treatment with edoxaban. Multiple clinical characteristics can help identify patients who should receive edoxaban. Further development and implantation of educational activities and management strategies are needed to ensure the correct use of edoxaban.

Aim The population included in randomized controlled clinical trial of ROCKET AF and observational studies were different, and the effectiveness and safety of rivaroxaban in stroke prevention of atrial fibrillation (AF) varied among studies. The aim of this study was to estimate the real-world outcomes of rivaroxaban in AF patients in a relatively accurate way. Methods A discrete event simulation (DES) model was proposed to predict the counterfactual outcomes of ROCKET AF that would have it been conducted in broader observational study populations. The hypothetical cohorts of patients were generated using Monte Carlo simulation. The DES model structure was built based on disease progression and possible outcomes of AF. Cardiovascular events were recorded during the simulated two-year follow-up period. Results The results showed lower predicted rates of stroke/ systemic embolism (SE) and major bleeding in three observational studies than those in simulated ROCKET AF. The simulated stroke/SE incidence was 1.097-1.318 per 100 patient-years and simulated major bleeding incidence was 2.804-3.238 per 100 patient-years in observational studies. The risk difference of stroke/SE and major bleeding was similar among predicted outcomes of the three observational studies. Most simulated hazard ratios (HRs) were close to the corresponding observed HRs. Conclusion The simulated incidence of stroke/SE incidence and major bleeding might reflect the real-world event rate in AF patients. Even some differences existed in the absolute rates of stroke/SE and major bleeding between observed and simulated studies, the results confirmed similar effectiveness and safety to ROCKET AF comparing rivaroxaban and warfarin in AF patients.