Direct oral anticoagulants (DOACs) have significant advantages over vitamin K antagonists including lack of need for routine laboratory monitoring. However, assessment of DOAC effect and concentration may be important to guide clinical management including need for DOAC reversal, particularly in acute or emergent situations. In this manuscript, the authors describe tests to screen for DOAC presence and tests that have demonstrated equivalence to gold standard testing for quantifying DOAC exposure. They also discuss the effect of DOACs on other coagulation assays and strategies for monitoring unfractionated heparin in patients with concomitant DOAC exposure.

UNASSIGNED: Direct oral anticoagulants (DOACs) have demonstrated clinical benefits and better patient adherence over low-molecular-weight heparin (LMWH) in treating patients with cancer-associated venous thrombosis (CAT). We aimed to compare the cost-effectiveness of DOACs against LMWH in patients with CAT from the perspective of the Hong Kong healthcare system.
UNASSIGNED: A Markov state-transition model was performed to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) for DOACs and LMWH in a hypothetical cohort of 10,000 patients with CAT over a 5-year lifetime horizon. The model was primarily based on the health states of no event, recurrent venous thromboembolism, bleeding, and death. Transition probabilities, relative risks, and utilities were derived from the literature. Resource cost data were obtained from the Hong Kong Hospital Authority. Deterministic and probabilistic sensitivity analyses tested the robustness of the results.
UNASSIGNED: Relative to LMWH, DOACs were associated with increased QALYs (1.52 versus 1.50) at a lower medical cost of USD 2,232 versus 8,224 in five years. The cost of LMWH was the main contributor to the outcome. Out of 10,000 simulated cases, DOACs were dominant in 15.8% and cost-effective in 42.1%, at the willingness-to-pay threshold of USD 148,392 per additional QALY.
UNASSIGNED: DOACs were associated with greater QALY improvements and lower overall costs compared to LMWH. Accounting for uncertainty, DOACs were between cost-effective and dominant in 57.9% of cases. DOACs are a cost-effective alternative to LMWH in the management of CAT in Hong Kong.

OBJECTIVE: Although prescription of direct oral anticoagulants (DOACs) for epileptic patients on anti-seizure medications (ASMs) is on the increase, international guidelines pose strict restrictions because this may lead to pharmacologic interactions. However, current evidence on their clinical relevance remains scanty. This retrospective, case-control study assessed the frequency of ischemic/hemorrhagic events and epileptic seizures involving DOAC-ASM cotherapy in the real world, compared with DOAC and ASM monotherapy, in age- and gender-matched controls.
METHODS: Data on patients who had been prescribed a concomitant DOAC and ASM therapy for at least 6 months were extracted from the database of the Pharmaceutical Service of the Alessandria Province (Italy). After exclusions, the case group included 124 patients, 44 on valproic acid (VPA) and 80 on levetiracetam (LEV) concomitant with a DOAC, and it was compared with the DOAC-control and ASM-control groups. The clinical and laboratory data were extracted from the electronic archives of the hospitals in the same province.
RESULTS: Two (1.6%) ischemic and 2 (1.6%) major hemorrhagic events were observed in the case group. Four (3.2%) ischemic and no hemorrhagic events occurred in the DOAC-control group. There were no statistically significant differences in the ischemic and hemorrhagic events between the case group (patients on concomitant LEV or VPA who were prescribed a DOAC) and the DOAC-control group, and there was no difference in the recurrence rate of epileptic seizures between the case group and the ASM-control group.
CONCLUSIONS: Although this study has some limits, mainly the small sample size, our findings indicate that neither LEV nor VPA concomitant treatment significantly affects the effects of DOACs in a real-world setting.

Direct oral anticoagulants (DOACs) are the standard treatment for thromboembolic protection in atrial fibrillation (AF) patients. Epigenetic modifications, such as DNA methylation and microRNAs, have emerged as potential biomarkers of AF. The epigenetics of DOACs is still an understudied field. It is largely unknown whether epigenetic modifications interfere with DOAC response or whether DOAC treatment induces epigenetic modifications. To fill this gap, we started the miR-CRAFT (Circulating microRNAs and DNA methylation as regulators of Direct Oral Anticoagulant Response in Atrial Fibrillation) research study. In miR-CRAFT, we follow, over time, changes in DNA methylation and microRNAs expression in naïve AF patients starting DOAC treatment. The ultimate goal of miR-CRAFT is to identify the molecular pathways epigenetically affected by DOACs, beyond the coagulation cascade, that are potentially mediating DOAC pleiotropic actions and to propose specific microRNAs as novel circulating biomarkers for DOAC therapy monitoring. We herein describe the study design and briefly present the progress in participant enrolment.

A notable increase in direct oral anticoagulant (DOAC) use has been observed in the last decade. This trend has surpassed the prescription of vitamin K antagonists (VKAs) due to the absence of the need for regular laboratory monitoring and the more favorable characteristics in terms of efficacy and safety. However, it is very common that patients on DOACs need an interventional or surgical procedure, requiring a careful evaluation and a challenging approach. Therefore, perioperative anticoagulation management of patients on DOACs represents a growing concern for clinicians. Indeed, while several surgical interventions require temporary discontinuation of DOACs, other procedures that involve a lower risk of bleeding can be conducted, maintaining a minimal or uninterrupted DOAC strategy. Therefore, a comprehensive evaluation of patient characteristics, including age, susceptibility to stroke, previous bleeding complications, concurrent medications, renal and hepatic function, and other factors, in addition to surgical considerations, is mandatory to establish the optimal discontinuation and resumption timing of DOACs. A multidisciplinary approach is required for managing perioperative anticoagulation in order to establish how to face these circumstances. This narrative review aims to provide physicians with a practical guide for DOAC perioperative management, addressing the most controversial issues.

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BACKGROUND: There is limited evidence to support definite clinical outcomes of direct oral anticoagulant (DOAC) therapy in chronic kidney disease (CKD). By identifying the important variables associated with clinical outcomes following DOAC administration in patients in different stages of CKD, this study aims to assess this evidence gap.
METHODS: An anonymised dataset comprising 97,413 patients receiving DOAC therapy in a tertiary health setting was systematically extracted from the multidimensional electronic health records and prepared for analysis. Machine learning classifiers were applied to the prepared dataset to select the important features which informed covariate selection in multivariate logistic regression analysis.
RESULTS: For both CKD and non-CKD DOAC users, features such as length of stay, treatment days, and age were ranked highest for relevance to adverse outcomes like death and stroke. Patients with Stage 3a CKD had significantly higher odds of ischaemic stroke (OR 2.45, 95% Cl: 2.10-2.86; p = 0.001) and lower odds of all-cause mortality (OR 0.87, 95% Cl: 0.79-0.95; p = 0.001) on apixaban therapy. In patients with CKD (Stage 5) receiving apixaban, the odds of death were significantly lowered (OR 0.28, 95% Cl: 0.14-0.58; p = 0.001), while the effect on ischaemic stroke was insignificant.
CONCLUSIONS: A positive effect of DOAC therapy was observed in advanced CKD. Key factors influencing clinical outcomes following DOAC administration in patients in different stages of CKD were identified. These are crucial for designing more advanced studies to explore safer and more effective DOAC therapy for the population.

Cancer-associated thrombosis (CAT) is an important prognostic factor for an increasing number of cancer patients. Understanding of CAT among cancer care providers has grown in recent years, and guidelines for the prevention and treatment of CAT have been published in Japan and around the world. In this article, we introduce these major guidelines and discuss differences we identified between the Japanese guidelines and those of other countries, with a focus on problems and issues. Insurance coverage of low-molecular-weight heparin and indications for primary prevention with direct oral anticoagulants in particular require urgent consideration.

BACKGROUND: Direct oral anticoagulants for the treatment of venous thromboembolism are supported by robust clinical trial evidence. Despite published guidance, general practitioners are faced with increasingly complex decisions and implementation remains sub-optimal in certain real-world scenarios.
METHODS: A two stage formal consensus exercise was performed to formulate consensus statements and a summary guide, facilitating optimal management of direct oral anticoagulants in venous thromboembolism patients by generalist physicians across Europe. An online questionnaire distributed to a broad panel (Phase 1), followed by a virtual panel discussion by an expert group (Phase 2) were conducted. Phase 1 statements covered nine management domains, and were developed via a literature review and expert steering committee. Participants rated statements by their level of agreement. Phase 1 responses were collated and analysed prior to discussion and iterative refinement in Phase 2.
RESULTS: In total 56 participants from across Europe responded to Phase 1. The majority had experience working as general practitioners. Consensus indicated that direct oral anticoagulants are the treatment of choice for managing patients with venous thromboembolism, at initiation and for extended treatment, with a review at three to six months to re-assess treatment effect and risk profile. Direct oral anticoagulant choice should be based on individual patient factors and include shared treatment choice between clinicians and patients; the only sub-group of patients requiring specific guidance are those with cancer.
CONCLUSIONS: Results demonstrate an appreciation of best practices, but highlight challenges in clinical practice. The patient pathway and consensus recommendations provided, aim to highlight key considerations for general practice decision making, and aid optimal venous thromboembolism treatment.

BACKGROUND: In patients undergoing revascularization for peripheral arterial disease (PAD), low-dose Factor Xa inhibitors (FXaI) taken with aspirin improved limb and cardiovascular outcomes compared to aspirin alone. Furthermore, in atrial fibrillation and venous thromboembolism, FXaI are recommended over vitamin K antagonists (VKA) for chronic anticoagulation. While studies have evaluated different perioperative anticoagulation regimens in patients treated for PAD, the optimal regimen for chronic anticoagulation in patients with PAD undergoing peripheral vascular intervention (PVI) has not been determined. This analysis compares outcomes of patients after PVI that require chronic anticoagulation with FXaI and VKA.
METHODS: The Vascular Quality Initiative-PVI database was used. Patients consistently treated with FXaI or VKA before the procedure, at discharge, and on long-term follow-up were defined as those receiving chronic anticoagulation. Patient demographics, procedural details, and perioperative and long-term outcomes were compared between FXaI and VKA groups.
RESULTS: A total of 109,268 patients were analyzed, and 6,885 were chronically anticoagulated with FXaI (N = 2,427) or VKA (N = 4,458). Patients anticoagulated with VKA were more frequently males (65.3% vs. 61.0%, P < 0.001) with end-stage renal disease (9.7% vs. 4.6%, P < 0.001) and more likely to be treated for chronic limb-threatening ischemia (58.1% vs. 52.7%, P < 0.001). Rates of hematoma following PVI were significantly higher in patients taking VKA compared to FXaI (3.5% vs. 1.9%, P < 0.001). Multivariable logistic regression analysis showed that VKA were associated with increased perioperative hematoma than FXaI (odds ratio = 1.89 [1.30-2.82]). Compared to patients taking VKA, those receiving FXaI had lower rates of major amputation (6.7% vs. 8.4%, P = 0.020) and mortality (7.6% vs. 15.2%, P ≤ 0.001). Using Kaplan-Meier analysis, patients consistently anticoagulated with FXaI had improved amputation-free survival after PVI. Adjusting for significant patient and procedural characteristics, Cox proportional hazard regression demonstrated that there is an increased risk for major amputation or mortality in patients using VKA compared to FXaI (hazard ratio 1.61, [1.36-1.90]).
CONCLUSIONS: Chronic anticoagulation with FXaI as compared to VKA was associated with superior perioperative and long-term outcomes in patients with PAD undergoing PVI. FXaI should be the preferred agents over VKA for chronic anticoagulation in patients with PAD undergoing PVI.