Safety Of Direct Oral Anticoagulants Research Articles

Efficacy and safety of DOACs versus LMWH for elderly patients with active cancer: A meta-analysis.

e13776 Background: Anticoagulant treatment in patients with cancer aims to reduce the high risk of thromboembolism. Direct oral anticoagulants (DOACs) and low-molecular-weight heparin (LMWH) are currently approved for the treatment of cancer-related thrombosis. However, there is limited data comparing the efficacy and safety of these two antithrombotic therapies among elderly patients with cancer. Methods: PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were systematically searched for studies comparing DOACs with LMWH in cancer patients with newly diagnosed venous thromboembolism (VTE) or pulmonary embolism (PE). Both solid tumors and hematologic malignancies were included. Outcomes of interest were recurrent VTE and major bleeding. Odds ratio (OR) with 95% confidence intervals (CI) were pooled with a random-effects model. Statistical analysis was performed with Review Manager 5.4.1. Heterogeneity was assessed using the I2 statistic and chi-squared test. Results: Four studies, three randomized controlled trials (RCTs) and one observational, were included. A total of 3,266 patients older than 65 years who underwent anticoagulation with DOACs (35%) or LMWH (65%) were incorporated in the analysis. There was no statistically significant difference between anticoagulation therapies for recurrent VTE (OR, 0.68; 95% CI, 0.41-1.11; p = 0.13; I² = 56%; Table) or major bleeding (OR, 1.18; 95% CI, 0.61-2.25; p = 0.08; I² = 60%; Table). Conclusions: Our findings suggest no statistically significant differences in recurrent VTE or major bleeding between DOACs and LMWH in elderly oncologic patients with newly diagnosed VTE or PE. Given the practical challenges of using LMWH, DOACs may be considered an alternative anticoagulation strategy for these patients. [Table: see text]

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants for Japanese Patients With Venous Thromboembolism - The Primary Results From the KUROSIO Study.

Direct oral anticoagulants (DOACs) are recommended as the first-choice anticoagulation therapy in the acute phase of venous thromboembolism (VTE). However, there is limited real-world data for Japanese VTE patients.Methods and Results: The KUROSIO study (UMIN000023747) was a prospective long-term observational study comprising 1,017 patients with concurrent acute symptomatic pulmonary thromboembolism and proximal deep vein thrombosis (DVT) or isolated calf DVT initially treated with DOACs. After excluding 24 patients, 993 (mean age, 66.3±15.1 years; 58.6% females) were analyzed. The incidences of recurrent symptomatic VTE and major bleeding for up to 52 weeks after diagnosis were 3.2% and 2.2%, respectively. Multivariate analyses revealed chemotherapy and anemia as significant risk factors associated with recurrent symptomatic VTE and major bleeding, respectively. The efficacy and safety of DOACs in Japanese patients with VTE were determined in this real-world observational study.

Direct oral anticoagulants versus vitamin K antagonists as stroke prevention in atrial fibrillation after cardiac surgery: a systematic review and meta-analysis

Abstract Background Cardiothoracic surgery guidelines advocate the use of vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) in the first days to months after major cardiac surgery. No recommendations on choice of anticoagulant in the first months after cardiac surgery have been issued since 2008, before the use of direct oral anticoagulants (DOACs). The basis for this is a lack of data on the safety and efficacy of DOACs after cardiac surgery. Purpose To systematically assess and meta-analyze the existing evidence on the effect of DOACs compared with VKAs on efficacy and safety after cardic surgery. We hypothesized that DOACs are non-inferior to VKAs in the setting of AF after cardiac surgery. Methods We searched Ovid MEDLINE, Ovid EMBASE, the Cochrane Central Register of Controlled trials and Clinicaltrials.gov from inception till 20 June 2023 and screened references in relevant reviews as grey literature search. Observational studies and randomized controlled trials comparing DOACs with VKAs for stroke prevention in patients with (postoperative) atrial fibrillation after cardiac surgery were included, focusing on procedures through thoracoscopy or thoracotomy. Outcomes of interest included thromboembolic events, all-cause stroke, major bleeding and mortality up to 6 months after cardiac surgery and admission duration. A random effects model was used to determine pooled treatment effects. The level of evidence was rated following the GRADE recommendations. Results We identified 4,146 records of which ten were included, together reporting on > 30,000 patients. There were no significant differences in thromboembolic events (OR 0.98; 95% CI 0.61-1.58; I^2 0%; GRADE: very low), all-cause stroke (OR 1.14; 95% CI 0.51-2.54; I^2 0%; GRADE: very low), major bleeding (OR 0.91; 95% CI 0.51-1.62; I^2 53%; GRADE: very low), all-cause mortality (OR 1.00; 95% CI 0.73-1.37; I^2 0%; GRADE: low), admission duration (MD -0.33; 95% CI -1.16 – 0.49; I^2 0%; GRADE: very low) between DOACs and VKAs in the first 6 months after cardiac surgery. Conclusion Efficacy and safety of DOACs as stroke prevention in AF following cardiac surgery were similar to that of VKAs in ten studies comprising more than 30,000 patients. Based on the existing literature, there is insufficient evidence to recommend one class of oral anticoagulants over another in the first months after cardiac surgery.Forest plot of primary outcomes

Real-world insights on anticoagulation therapies in non-valvular atrial fibrillation: a comprehensive electronic health record-based study using natural language processing and machine learning

Abstract Background Limited evidence exists regarding real-world practices and outcomes of oral anticoagulation in patients with Non-Valvular Atrial Fibrillation (NVAF). Purpose To conduct a retrospective real-world data (RWD) study using Natural Language Processing (NLP) and Machine Learning (ML) on Electronic Health Records (EHRs) to evaluate the efficacy and safety of Direct Oral Anticoagulants (DOACs) and vitamin K antagonists (VKAs) in NVAF patients. Methods Retrospective study in 15 Spanish hospitals between 2014-2020 including adult NVAF patients treated with oral anticoagulants without anticoagulation history, recent thrombotic events, rheumatic mitral valvular heart disease, mitral valve stenosis, venous thromboembolism, nor pregnancy. We employed EHRead®, a free text analysis engine utilizing NLP and ML to extract RWD from EHRs based in SNOMED CT (standardized coding system). Free-text information was extracted and organized in an anonymized database for population-based descriptive and comparative analysis. After matching patients using propensity-score matching (PSM), we used Kaplan-Meier curves to compare VKA vs DOAC efficacy on thrombotic prevention, safety, and mortality. Results After evaluating 138,773,332 EHRs from 4.6 million patients, 44,292 NVAF patients were included; 35,267 (79.6%) treated with VKA and 9,025 (20.4%) with DOAC. Half of them were men (53.0%) with a mean (SD) age of 76.3 (12.7) years. VKA-treated patients tended to be older, with more cardiovascular comorbidities and higher CHA2DS2-VASc scores than DOACs-treated patients (Table 1). Using PSM, 8,930 patients were matched per subgroup with standardized mean differences below 10% for all confounders. The comparative analysis showed that DOAC-treated patients had a significant lower risk of thrombotic, minor bleeding events, and mortality than VKA-treated ones, with no significant differences in major bleeding (Figure 1). Conclusion The application of NLP and ML allowed us to create an extensive, plausible, and detailed database of Spanish NVAF patients from RWD in EHRs. In our cohort, we found a higher efficacy and lower mortality and minor bleeding events with DOACs over VKAs, without differences in major bleeding events. This study was sponsored by Pfizer and Bristol Myers Squibb. JCS, MA & CS were paid consultants to Pfizer and Bristol Myers Squibb in connection with the development of this abstract. CAC & LMS are employes of the SAVANA who were paid consultants to Pfizer and Bristol Myers Squibb in connection with the development of this abstract. DA & SFC are employees of Pfizer.Table 1Figure 1

#280 Effectiveness and safety of direct oral anticoagulants vs VKA in patients on chronic dialysis: a target trial emulation using nationwide registry data

Abstract Background and Aims The mortality and morbidity rates among patients on dialysis remain high and cardiovascular disease is the leading cause of death in this population. In chronic kidney disease (CKD), a major thromboembolic risk is paradoxically associated with a major haemorrhagic risk. Hence, the prescription of oral anticoagulants in CKD patients is challenging. Clinical trials of direct oral anticoagulants (DOAC) are scarce and inconclusive in patients who are receiving dialysis, for whom DOAC are not labelled in Europe. In an exhaustive French nationwide registry of patients undergoing chronic dialysis, we compared the effectiveness and safety of off-label DOAC use versus approved vitamin K antagonist (VKA). Method Data on patients on dialysis were extracted from the French Renal Epidemiology and Information Network (REIN) registry and merged with data from the French national healthcare system database (Système National des Données de Santé, SNDS). Patients on dialysis who had initiated treatment with an oral anticoagulant between January 1st, 2012, and December 31st, 2020, were eligible for inclusion. The primary safety outcome was the occurrence of major bleeding events and the primary effectiveness outcome was the occurrence of thrombotic events. Using target trial emulation design, we compared the safety and effectiveness outcomes for DOAC and VKA using propensity-score-weighted cause-specific Cox regression. Results 8 954 patients received an oral anticoagulant (483 DOAC and 8 471 VKA) for the first time after the initiation of dialysis. Over a median [interquartile range] follow-up period of 1.7 [0.8-3.2] years, 2 567 patients presented a first thromboembolic event and 1 254 patients had a bleeding event. After propensity score adjustment, the risk of a thromboembolic event was significantly lower in patients treated with a DOAC than in patients treated with a VKA (weighted hazard ratio (HR) [95% confidence interval (CI)]: 0.66 [0.46; 0.94] (Figure). A non-significant trend toward lower risk of major bleeding events was found in patients treated with a DOAC compared to patients treated with a VKA (weighted HR [95% CI]: 0.68 [0.41; 1.12]) (Figure). Sensitivity analyses showed the same trends. Conclusion The fact that patients on dialysis are excluded from large, cardiovascular-disease-focused randomized controlled trials (such as those with DOACs) significantly limits the evidence needed to make clinical decisions. Most of the retrospective cohort studies comparing these two drug classes were performed in the USA, where, in contrast to Europe, apixaban has been approved for the treatment of non-valvular fibrillation in patients on haemodialysis. Our real-world study of patients on dialysis is one of the first of its type to have assessed the effectiveness and safety of off-label DOAC prescription (relative to VKA prescription) in Europe. In a large group of dialysis patients initiating oral anticoagulation, the off-label use of DOACs was associated with a statistically significant lower risk of thromboembolic events, and a non-significant trend toward lower risk of bleeding relative to VKA use. These results are reassuring with regard to the off-label use of DOACs and might facilitate the establishment of an expert consensus and guidelines on antithrombotic therapy in patients with ESKD.

Efficacy and Safety of Direct Oral Anticoagulants for Acute Treatment of Venous Thromboembolism in Older Adults: A Network Meta-Analysis of Randomised Controlled Trials.

This systematic review and network meta-analysis aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in adults aged 75 and over undergoing acute venous thromboembolism (VTE) treatment. PubMed, Embase and the CENTRAL were searched up to 25 December 2023. The incidence of VTE recurrence and bleeding events was assessed. Employing a frequentist network meta-analysis approach, interventions not directly compared could be indirectly assessed through the 95% confidence interval (CI), enhancing the interpretability of the search results. The surface under the cumulative ranking curves (SUCRA) was utilized to generate the relative ranking probabilities for each group. Our study, analysing 6 randomised controlled trials with 3665 patients, compares direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in adults aged 75 and over with acute venous thromboembolism. Edoxaban reduces VTE recurrence risk compared with VKAs (risk ratio [RR] .50, 95% CI 0.27 - .95), while apixaban significantly decreases bleeding risk compared with VKAs (RR .23, 95% CI 0.08 - .69), edoxaban (RR .28, 95% CI 0.09 - .86) and rivaroxaban (RR .28, 95% CI 0.09 - .86). Despite low overall evidence quality, apixaban consistently ranks highest for both efficacy and safety. Findings underscore the nuanced efficacy-safety balance in this population, emphasizing cautious interpretation due to evidence limitations. Apixaban emerges as a favourable choice for acute VTE treatment in the elderly, displaying reduced bleeding risk compared to other treatments while maintaining comparable efficacy. Future studies should explore diverse anticoagulants efficacy and safety in older populations. Additionally, clinical prediction models tailored to geriatric cohorts are crucial for guiding treatment duration decisions.

Safety of DOACs in patients with Child-Pugh Class C cirrhosis and trial fibrillation.

Anticoagulation (AC) is used for stroke prevention in atrial fibrillation (AF). Direct Oral Anticoagulants (DOACs) are safe in patients with AF without cirrhosis, they are hardly studied in patients with advanced cirrhosis. Our study evaluates the safety and outcomes of DOACs in patients with Child-Pugh class C cirrhosis (CPC). We queried TriNetX Database. Patients with CPC and AF were divided into three cohorts: patients on DOACs, no AC, and warfarin. Three study arms were created using a 1:1 propensity score matching system (PSM). Totally 16 029 patients met the inclusion criteria. Of those, 20.2% (n = 3235) were on DOACs, 47.1% (n = 7552) were not on AC, and 32.7% (n = 5242) were on warfarin. First arm comparing AC versus no AC, a statistically significant benefit was identified in 3-year mortality risk (47% vs 71%, P < 0.0001) and transplant status (17% vs 5%, p < 0.0001) with AC. However, no significant difference was identified regarding intracranial hemorrhage and GI bleeding risk. Second arm comparing patients on DOACs versus no AC, we identified mortality benefit (40% vs 72%, P < 0.0001) and a higher transplant rate (9% vs 3.2%, P < 0.0001) with DOACs. Intracranial hemorrhage rates (6% vs 4%, P = 0.03) were higher in patients on DOACs. Third arm comparing patients on DOACs versus Warfarin, a statistically significant lower risk of intracranial hemorrhage (6.6% vs 8.7%, P = 0.004) and GI bleed (2% vs 2.4%, P < 0.0001) were identified in patients on DOACs. Anticoagulation is safe in patients with CPC with AF and may provide a mortality benefit. DOACs are a safer alternative to warfarin.

DOACs for Older adults with Atrial Fibrillation and Falls: Results from the prospective single-centre DOAFF study

IntroductionFalls are one of the most fearsome events in anticoagulated older adults. The evidence concerning safety of direct oral anticoagulants (DOACs) in falling elderly patients with atrial fibrillation (AF) is still limited. MethodsWe prospectively enrolled consecutive anticoagulant-naïve patients aged 65 years and older, starting anticoagulation with DOACs for AF. The study cohort was stratified in fallers vs. non-fallers, according to the occurrence of at least one fall during the 2-year follow-up and bleeding outcomes were evaluated. ResultsWe enrolled 524 consecutive patients. Mean age was 80.8 years and they were mostly women (54.0%). Among the study cohort, 148 patients (28.2%) presented at least one fall episode during the study period. After the adjustment for potential confounders, no difference was found between fallers and non-fallers for all the study outcomes: major bleeding [HR: 1.04 (95%CI: 0.58–1.85)], intracranial haemorrhage [HR: 1.63 (95%CI: 0.69–3.80)], clinically relevant non-major bleeding [HR: 1.21 (95%CI: 0.83–1.76)], and all-cause death [HR: 1.51 (95%CI: 0.85–2.69)]. The presence of a prior cerebrovascular event [HR: 2.27 (95%CI: 1.12–4.62); p-value: 0.02] and polypharmacy [HR: 1.60 (95%CI: 1.08–2.39); p-value: 0.02] were the main drivers for major and clinically relevant non-major bleedings, respectively. ConclusionsFalls in an anticoagulant-naïve population aged 65 years and over starting a DOAC for AF do not increase the bleeding risk. Thus, the presence of falls should not discourage clinicians from prescribing DOACs also in this subset of patients.

The efficacy and safety of direct oral anticoagulants in the treatment of the acute phase of heparin-induced thrombocytopenia: A systematic review.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. To investigate the safety and efficacy of direct oral anticoagulants (DOACs) in the treatment of the acute phase of heparin-induced thrombocytopenia (HIT). A systematic review of the literature was conducted on PubMed, MEDLINE, Embase, and Web of Science Core Collection through July 2023. Search terms included "heparin-induced thrombocytopenia AND direct-oral-anticoagulants" in addition to a list of oral anticoagulants. Adult patients who used direct oral anticoagulants as the initial treatment for the acute phase of HIT were included. A total of 1,188 articles were initially identified, with 770 articles reviewed following removal of duplicates. Following the application of inclusion and exclusion criteria, 12 articles were ultimately included. Rivaroxaban was the most-utilized DOAC (28 patients), followed by apixaban (7 patients) and dabigatran (1 patient). All patients with thrombocytopenia demonstrated successful platelet recovery, with two patients presenting with normal platelet counts. One patient developed a deep venous thrombosis with no other new or recurrent thromboses. There were no reported clinically significant adverse events in any patient. Obstacles and deterrents to the use of the standards of care in the acute phase of HIT exist. Argatroban and bivalirudin require intravenous infusion and require close aPTT monitoring and dose adjustment. Fondaparinux requires injection and is contraindicated with body weight <50kg. DOACs would offer the novel ability for an oral treatment in the treatment of the acute phase HIT and allow for minimal monitoring and consistent dosing strategies. Therefore, DOACs are an intriguing choice for the treatment of the acute phase of HIT. Data from 12 publications and across 36 patients suggests that the use of DOACs in the acute phase of HIT may be a safe and efficacious treatment option with favorable ease of monitoring and management.

Oral anticoagulants versus vitamin K antagonists in the treatment of non-valvular atrial fibrillation in patients with stage 4-5 chronic kidney disease

Aim. To compare the effectiveness and safety of direct oral anticoagulants (DOACs) with a vitamin K antagonist (VKA) in patients with atrial fibrillation (AF) and stage 4 and 5 chronic kidney disease (CKD).Material and methods. We searched in the PubMed, Google Scholar, and Web of Science databases from 1990 to 2022 for studies that compared DOACs with VKAs in patients with AF and stage 4 and 5 CKD. The patient, intervention, comparison, outcome (PICO) search strategy was used. Data were extracted by independent researchers and meta-analyzed.Results. A total of 6 studies were included in this meta-analysis. In terms of effectiveness, DOACs were comparable to VKAs. In terms of safety, DOACs and VKAs also had no statistical differences in hemorrhagic stroke, minor/gastrointestinal bleeding, overall mortality, but there was statistical significance in major bleeding. Conclusion. In terms of efficacy and safety, in general, DOACs were comparable to VKAs, but there were a number of following differences: the administration of DOACs to patients with stage 4 and 5 CKD, as well as those on hemodialysis, was accompanied by a significant reduction in the number of major bleedings, compared with warfarin therapy.

Long-Term Efficacy and Safety of Direct Oral Anticoagulants at Reduced Doses in the Secondary Prevention of Venous Thromboembolism and Post-Thrombotic Syndrome.

Background: Anticoagulation for venous thromboembolism (VTE) is required for at least three to six months; however, it is advisable to extend the duration in certain cases, in which case a reduced dose of Direct Oral Anticoagulants (DOACs) may be an option. Our objective was to investigate the efficacy and safety of reduced-dose DOACs in extended anticoagulation treatment compared to full doses. Methods and Results: This retrospective single-centre study included 185 patients treated with DOACs for at least 6 months who were divided into two groups: (1) the Full Dose (FD) group (n = 113) and (2) the Reduced Dose (RD) group (n = 72), which included patients treated with Apixaban at 2.5 mg bis in die (BID) and Rivaroxaban at 10 mg once daily (OD). Post-thrombotic syndrome (PTS) and its progression were evaluated. During an overall follow-up of 48.32 ± 29.49 months, no VTE occurred, and no patients experienced major bleeding; clinically relevant non-major bleeding occurred in three patients in each group (2.7% vs. 4.2% in FD vs. RD, respectively, p = 0.57). From baseline to follow-up, the prevalence of PTS was not significantly decreased in either group (FD: 54.9% vs. 51.3%, p = 0.29; RD 51.4% vs. 44.4%, p = 0.12); conversely, the Villalta score values were significantly decreased at the last follow-up (FD: 5.51 ± 4.18 vs. 5.51 ± 4.18, p < 0.001; RD 5.49 ± 4.06 vs. 5.11 ± 3.73, p = 0.006). Conclusion: In this real-world retrospective registry, very long-term extended anticoagulant therapy with DOACs at full or reduced doses showed comparable efficacy, safety, and impact on PTS progression. Larger studies are needed.

Efficacy and safety of dabigatran and rivaroxaban in atrial fibrillation patients with impaired liver function: a multicenter retrospective cohort study.

The efficacy and safety of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with impaired liver function (ILF) have not been sufficiently studied. The aim of this study was to evaluate the efficacy and safety of DOACs for stroke prevention in patients with AF and ILF. This study was based on data from 15 centers in China, including 4,982 AF patients. The patients were divided into 2 subgroups based on their liver function status: patients with normal liver function (NLF)(n = 4213) and patients with ILF (n = 769). Logistic regression analysis was used to investigate the risk of total bleeding, major bleeding, thromboembolism, and all-cause deaths in AF patients with NLF and ILF after taking dabigatran or rivaroxaban, respectively. Among AF patients treated with dabigatran or rivaroxaban, patients with ILF were associated with significantly higher major bleeding, compared with NLF patients (aOR: 4.797; 95% CI: 2.224-10.256; P < 0.001). In patients with NLF, dabigatran (n = 2011) had considerably lower risk of total bleeding than rivaroxaban (n = 2202) (aOR: 1.23; 95% CI: 1.002-1.513; P = 0.049). In patients with ILF, dabigatran (n = 321) significantly favored lower risks of major bleeding compared with rivaroxaban(n = 448) (aOR: 5.484; 95% CI: 1.508-35.269; P = 0.026). After using dabigatran or rivaroxaban, patients with ILF had remarkably increased risk of major bleeding compared with patients with NLF. In AF patients with NLF, dabigatran had the distinct strength of significantly reduced risk of total bleeding compared with rivaroxaban. In patients with AF and ILF, dabigatran use was associated with lower risk for major bleeding compared with rivaroxaban.

Comparison of Effectiveness and Safety of Direct-Acting Oral Anticoagulants and Vitamin K Agonists in Patients With Atrial Fibrillation and End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

The objective of the study is mentioned, but it could be further clarified by explicitly stating the aim to compare the effectiveness and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) specifically in patients with atrial fibrillation (AF) and end-stage renal disease (ESRD).We conducted a thorough electronic search of the literature, encompassing databases such as PubMed, EMBASE, Cochrane Library, and Web of Science from their inception up to March 5, 2024. Furthermore, we meticulously examined the bibliographies of included studies to identify additional relevant literature. The reporting of this meta-analysis adhered to the guidelines outlined in the Preferred Reporting of Systematic Review and Meta-analysisguidelines. The endpoints evaluated in this meta-analysis included all-cause mortality, stroke or systemic embolism, and major bleeding. Data analysis was carried out utilizing RevMan Version 5.4 (Cochrane, London, United Kingdom). Dichotomous outcomes, including all-cause mortality, stroke or systemic embolism, and major bleeding, were presented as risk ratios (RRs) with corresponding 95% confidence intervals (CI). A total of 11 studies were incorporated in this meta-analysis, comprising a pooled sample size of 44,863 participants with AF. The pooled analysis revealed no significant disparity between DOACs and VKAs concerning stroke or systemic embolism (RR: 0.93, 95% CI: 0.77 to 1.14) and all-cause mortality (RR: 0.86, 95% CI: 0.74 to 1.00). However, there was a noteworthy reduction in the risk of major bleeding events associated with DOACs compared to VKAs (RR: 0.84, 95% CI: 0.73 to 0.96). Consequently, DOACs may be considered a viable alternative to warfarin in patients with ESRD. However, we need further larger clinical trials to validate these findings.

Direct Oral Anticoagulation in Lung Transplant Recipients.

Presently, the management of direct oral anticoagulants lacks specific guidelines for patients before and after transplant, particularly for lung transplant recipients. We aimed to consolidate the existing literature on direct oral anticoagulants and explore their implications in lung transplant recipients. We conducted a comprehensive search in PubMed and Google Scholar databases for studies published between January 2000 and December 2022, using specific search terms. We only included studies involving lung transplant recipients and focusing on direct oral anticoagulants. Five relevant publications were identified, providing varied insights. None of the studies specifically addressed bleeding complications associated with direct oral anticoagulants in lung transplant recipients. Limited details were available on the type of solid-organ transplant or the specific direct oral anticoagulant used in these studies. Varied bleeding complications associated with direct oral anticoagulants in lung transplant recipients were reported, but studies lacked specificity on transplant type and direct oral anticoagulant variations. Notably, the incidence of venous thrombotic embolism in lung transplant recipients was comparatively higher than in other solid-organ transplant recipients, potentially linked to factors such as corticosteroid therapy, calcineurin inhibitors, and cytomegalovirus infections. Our synthesis on findings of use of direct oral anticoagulant in lung transplant recipients emphasized challenges of managing these medications in urgent transplant situations. Recommendations from experts suggested caution in initiation of direct oral anticoagulants posttransplant until stability in renal and hepatic function is achieved. The limited evidence on safety of direct oral anticoagulants in lung transplant recipients underscores the need for further research and guidance in this specific patient population.

Effectiveness and safety of direct oral anticoagulants among patients with non-valvular atrial fibrillation and liver disease: A multinational cohort study

Background and aimsThe effects of direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (NVAF) and liver disease remain poorly understood. Our multinational cohort study assessed the effectiveness and safety of DOACs in this high-risk population. MethodsWe assembled two population-based cohorts in United Kingdom and in Québec of NVAF patients with liver disease initiating DOACs or vitamin K antagonists (VKAs) between 2011 and 2020. Using an as-treated exposure definition, we compared DOACs to VKAs and apixaban to rivaroxaban. After inverse probability of treatment weighting, Cox proportional hazards models estimated site-specific hazard ratios (HRs) and 95 % confidence intervals (CIs) of ischemic stroke and major bleeding. Site-specific estimates were pooled using random-effects models. Analyses were repeated among NVAF patients with cirrhosis. ResultsThere were 11,881 NVAF patients with liver disease (2683 with cirrhosis). Among those, 8815 initiated DOACs (4414 apixaban, 2497 rivaroxaban) and 3696 VKAs. The HRs (95 % CIs) for DOACs compared to VKAs were 1.01 (0.76–1.34) for ischemic stroke and 0.87 (0.77–0.99) for major bleeding. Results were consistent among patients with cirrhosis. The HRs (95 % CIs) for apixaban compared to rivaroxaban were 0.85 (0.60–1.20) for ischemic stroke and 0.80 (0.68–0.95) for major bleeding. This decreased bleeding risk was not observed among patients with cirrhosis (HR, 1.01; 95 % CI 0.72–1.43). ConclusionsAmong NVAF patients with liver disease, DOACs were as effective and slightly safer than VKAs, and apixaban was as effective but safer than rivaroxaban. The safety benefit with apixaban was not present among patients with cirrhosis.

Recommendations for the safe use of direct oral anticoagulants in patients with cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data.

The popularity of direct oral anticoagulants (DOACs) is increasing among patients with cirrhosis. Cirrhosis has a major impact on the pharmacokinetics of drugs,potentially increasing adverse events. Safe useof drugs in cirrhosis requires a diligent risk-benefit analysis. The aim of this study is to develop practice recommendations for safe use of DOACs in cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data. We conducted a systematic literature search to identify studies on pharmacokinetics, pharmacodynamics and safety of DOACs in cirrhosis. Data were collected and presented in summary tables by severity of cirrhosis using the Child-Turcotte-Pugh (CTP) classification. A multidisciplinary expert panel evaluated the results and classified the DOACs according to safety. Fifty four studies were included. All DOACs were classified as 'no additional risks known' for CTP A. For CTP B, apixaban, dabigatran and edoxaban were classified as 'no additional risks known'. Apixaban and edoxaban showed fewer adverse events in patients with cirrhosis, while dabigatran may be less impacted by severity of cirrhosis based on its pharmacokinetic profile. Rivaroxaban was classified as 'unsafe' in CTP B and C based on significant pharmacokinetic alterations. Due to lack of data, apixaban, dabigatran and edoxaban were classified as 'unknown' for CTP C. DOACs can be used in patients with CTP A cirrhosis, and apixaban, dabigatran and edoxaban can also be used in CTP B. It is recommended to avoid rivaroxaban in CTP B and C. There is insufficient evidence to support safe use of other DOACs in CTP C cirrhosis.

Efficacy and safety of direct oral anticoagulants versus low-molecular-weight heparin for thromboprophylaxis after cancer surgery: a systematic review and meta-analysis.

Direct oral anticoagulants (DOACs) used as an alternative to low-molecular-weight heparin (LMWH) for thromboprophylaxis after cancer surgery for venous thromboembolic events (VTE) remains unclear. This study aimed to investigate the efficacy and safety of DOACs versus LMWH in these patients. A search of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science was carried out and included all randomized controlled trials (RCTs) and observational studies that directly compared DOACs with LMWH for thromboprophylaxis in patients after cancer surgery through July 25, 2023. The primary efficacy and safety outcomes were VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB) within 30days of surgery. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) tool for RCTs and ROBINS-I tool for non-randomized studies. This study was registered in PROSPERO (CRD42023445386). We retrieved 5149articles, selected 27 for eligibility, and included 10 studies (three RCTs and seven observational studies) encompassing 3054 patients who underwent postoperative thromboprophylaxis with DOACs (41%) or LMWH (59%). Compared to LMWH thromboprophylaxis, DOACs had a comparable risk of VTE (RR:0.69[95% CI:0.46-1.02], I2 = 0%), major bleeding (RR:1.55 [95% CI:0.82-2.93], I2 = 2%), and CRNMB (RR, 0.89 [95% CI, 0.4-1.98], I2 = 31%) during the 30-day postoperative period. Subgroup analysis of VTE and major bleeding suggested no differences according to study type, extended thromboprophylaxis, tumor types, or different types of DOAC. DOACs are potentially effective alternatives to LMWH for thromboprophylaxis in patients undergoing cancer surgery, without increasing the risk of major bleeding events.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants Compared with Warfarin in Patients with Low Bodyweight who have Atrial Fibrillation: ASystematic Review and Meta-analysis.

oral anticoagulant (DOAC) agents are becoming the anticoagulation strategy of choice for most clinical risks for which they are indicated. However, residual uncertainty remains regarding their use in preventing stroke in patients with low bodyweight [< 60 kg or body mass index (BMI) < 18 kg/m2]. We have carried out pooled systematic analyses of published studies to determine the efficacy and safety of these agents compared with warfarin in stroke prevention in patients with low bodyweight. We carried out a comprehensive search of electronic databases from inception to June 2023 for eligible studies reporting on the efficacy and safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation who had low bodyweight. These include PubMed, EMBASE, the Cochrane Database of Systematic Reviews, the Science Citation Index, and the Database of Abstracts of Reviews of Effectiveness. Using the random effects model, derived pooled odd ratios (with their corresponding confidence intervals) of mortality outcomes in patient cohorts exposed to direct oral anticoagulants versus warfarin in patients with atrial fibrillation who had low bodyweight. Nine studies (n = 159,514 patients) were included in our meta-analysis. DOAC analogs were associated with lower stroke recurrence compared with warfarin [odds ratio (OR) 0.66, 95% confidence interval (CI) 0.49-0.9]; however, there was no significant difference in the composite outcome (OR 0.81, 95% CI 0.59-1.09) and mortality (OR 0.82, 95% CI 0.48-1.41). Additionally, DOAC analogs showed a significant reduction in major bleeding events by 30% compared with warfarin (OR 0.70, 95% CI 0.62-0.80). In this pooled meta-analytical synthesis of studies comprising both real-world and randomized controlled data, the use of DOAC analogs in patients with atrial fibrillation and low bodyweight (< 60 kg or BMI < 18 kg/m2) was associated with a significant reduction in risks of stroke and major bleeding compared with patient cohorts stabilized on warfarin-based therapy. There was uncertainty regarding the composite outcome and mortality point estimate between these two anticoagulation strategies. This finding helps to resolve the uncertainty associated with the use of DOACs in this cohort. Additionally, it suggests the need for confirmatory non-inferiority randomized controlled trials evaluating DOACs versus warfarin in this cohort of patients.

Effectiveness and safety of direct oral anticoagulants versus vitamin K antagonists in patients on chronic dialysis: a nationwide registry study.

Clinical trials of direct oral anticoagulants (DOAC) are scarce and inconclusive in patients who are receiving dialysis, for whom DOAC are not labelled in Europe. In a French nationwide registry study of patients on chronic dialysis, we compared the effectiveness and safety of off-label DOAC use vs. approved vitamin K antagonist (VKA). Data on patients on dialysis were extracted from the French Renal Epidemiology and Information Network (REIN) registry and merged with data from the French national healthcare system database (Système National des Données de Santé, SNDS). Patients on dialysis who had initiated treatment with an oral anticoagulant between January 1st, 2012, and December 31st, 2020, were eligible for inclusion. The primary safety outcome was the occurrence of major bleeding events and the primary effectiveness outcome was the occurrence of thrombotic events. Using propensity-score-weighted cause-specific Cox regression, we compared the safety and effectiveness outcomes for DOAC and VKA. 8,954 patients received an oral anticoagulant (483 DOAC and 8,471 VKA) for the first time after the initiation of dialysis. Over a median [interquartile range] follow-up period of 1.7 [0.8-3.2] years, 2,567 patients presented a first thromboembolic event and 1,254 patients had a bleeding event. After propensity score adjustment, the risk of a thromboembolic event was significantly lower in patients treated with a DOAC than in patients treated with a VKA (weighted hazard ratio (wHR) [95% confidence interval (CI)]: 0.66 [0.46; 0.94]. A non-significant trend toward a lower risk of major bleeding events was found in DOAC-treated patients, relative to VKA-treated patients (wHR [95%CI]: 0.68 [0.41; 1.12]). The results were consistent across subgroups and in sensitivity analyses. In a large group of dialysis patients initiating an oral anticoagulant, the off-label use of DOACs was associated with a significantly lower risk of thromboembolic events and a non-significantly lower risk of bleeding, relative to VKA use. This provides reassurance regarding the off-label use of DOACs in people on dialysis.

Oral Anticoagulation and Mortality in Cases with Intracranial Bleeding: Analysis of Nationwide Prescription and Hospitalization Data.

To demonstrate the safety of direct oral anticoagulants in relation to intracranial bleeding (ICB), we compared the number of patients taking anticoagulants in all cases of hospitalization and cases of hospitalization for ICB over time in Germany. We analyzed the intrahospital mortality of ICB cases in relation to long-term use of anticoagulants (LUAs).We performed a retrospective registry analysis of nationwide German hospitalizations including all hospital admissions and admission for ICB in patients aged ≥60 years in the period from 2006 to 2020 and separated for LUAs. In 2006, the age-standardized rate of hospitalized male patients with LUAs was 7.3% and that of female patients was 5.6%. In 2020, the rates increased to 22.0 and 17.7% for male and female patients, respectively. Among patients hospitalized for ICB in 2006, 7.0 and 5.6% were male and female patients with LUAs, respectively. In 2020, the rate increased to 13.7% for males and 10.8% for females.In 2006, age-standardized mortality rates of male and female patients with ICB without LUAs were 24.1 and 23.9%, respectively. In 2020, the rate slightly decreased to 22.7% in males, but it remained almost unchanged in females at 23.8%. In the cases with LUA, the mortality rate decreased from 30.1 to 24.3% in males and from 28.4 to 24.2% in females in the same period. LUA seems to be safe because there is a slower increase of the rate of LUAs in ICB cases than in generally hospitalized cases in the period from 2006 to 2020. In addition, mortality in ICB cases with LUA tends to decrease compared to cases without LUA.