Non-vitamin K Antagonist Oral Anticoagulants and Drug-Food Interactions: Implications for Clinical Practice and Potential Role of Probiotics and Prebiotics

Non-vitamin K antagonist oral anticoagulants (NOACs) are a therapeutic option to prevent stroke in patients with atrial fibrillation (AF). In fact, NOACs have become the recommended choice by international clinical practice guidelines over vitamin K antagonists (VKA), because of their efficacy and safety profile, especially in newly initiated patients. The more predictable pharmacokinetic and pharmacodynamic profile of this family of drugs allows preventing anticoagulation drug monitoring. Furthermore, NOACs have significantly fewer drug and food interactions in comparison with VKAs. Despite this, there are no studies that compare the effects on the quality of anticoagulation of NOACs with the intake of potential interactions drugs of P-glycoprotein and cytochrome P450 (CYP). This review brings an overview of NOACs pharmacokinetics profile and their potential drug-food interactions. We also briefly discuss the potential role of prebiotics and probiotics in patients under therapy with NOACs.

Clinical and laboratory testing of oral anticoagulation therapy vitamin k antagonists at the emergency department of Hanoi Heart Hospital

Background: The most commonly used oral anticoagulant is acenocoumarol with the brand name is Sintrom and recently, warfarin with the brand name is Coumadin has begun to be used. Anticoagulation with vitamin K antagonists faces two main obstacles: the narrow therapeutic range and the effectiveness of the drug varies by many factors. Objective: " Current status of coagulation disorders in the treatment of anticoagulants with vitamin K antagonists. Understanding some factors affecting the goal of anticoagulant treatment". Method: Cross-sectional, retrospective, descriptive analysis of drug use and influencing factors of patients diagnosed with coagulopathy admitted to the emergency department at Hanoi Heart Hospital from April 2020 to August 2021. Results: There were 675 patients admitted to the hospital with blood clotting disorders. The average age is 60,17±10,13, the youngest is 30, the oldest is 90; 63 patients, accounting for 9.42%, need to be hospitalized for inpatient treatment; There are 108 patients, accounting for 16%, with bleeding and 18 patients, accounting for 2.7%, with thromboembolism or valve obstruction. Conclusion: Coagulation disorders during treatment with vitamin K antagonist anticoagulants is a common condition in the emergency department. However, the complication rate is not high. There are many factors that affect the patient's treatment goals and the drug use is a fairly common factor.

A systematic review of the evidence supporting post-operative antithrombotic use following cardiopulmonary bypass in children with CHD

Objectives: To determine the optimal antithrombotic agent choice, timing of initiation, dosing and duration of therapy for paediatric patients undergoing cardiac surgery with cardiopulmonary bypass. Methods: We used PubMed and EMBASE to systematically review the existing literature of clinical trials involving antithrombotics following cardiac surgery from 2000 to 2020 in children 0–18 years. Studies were assessed by two reviewers to ensure they met eligibility criteria. Results: We identified 10 studies in 1929 children across three medications classes: vitamin K antagonists, cyclooxygenase inhibitors and indirect thrombin inhibitors. Four studies were retrospective, five were prospective observational cohorts (one of which used historical controls) and one was a prospective, randomised, placebo-controlled, double-blind trial. All included were single-centre studies. Eight studies used surrogate biomarkers and two used clinical endpoints as the primary endpoint. There was substantive variability in response to antithrombotics in the immediate post-operative period. Studies of warfarin and aspirin showed that laboratory monitoring levels were frequently out of therapeutic range (variably defined), and findings were mixed on the association of these derangements with bleeding or thrombotic events. Heparin was found to be safe at low doses, but breakthrough thromboembolic events were common. Conclusion: There are few paediatric prospective randomised clinical trials evaluating antithrombotic therapeutics post-cardiac surgery; most studies have been observational and seldom employed clinical endpoints. Standardised, validated endpoints and pragmatic trial designs may allow investigators to determine the optimal drug, timing of initiation, dosing and duration to improve outcomes by limiting post-operative morbidity and mortality related to bleeding or thrombotic events.

Use of Direct Oral Anticoagulant and Outcomes in Patients With Atrial Fibrillation after Transcatheter Aortic Valve Replacement: Insights From the STS/ACC TVT Registry

Background Clinical evidence on the safety and effectiveness of using direct oral anticoagulants (DOACs) in patients with atrial fibrillation after transcatheter aortic valve replacement (TAVR) remains limited. The aim of this study was to investigate the trends and outcomes of using DOACs in patients with TAVR and atrial fibrillation. Methods and Results Data from the STS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) Registry was used to identify patients who underwent successful TAVR with preexisting or incident atrial fibrillation who were discharged on oral anticoagulation between January 2013 and May 2018. Patients with a mechanical valve, valve‐in‐valve procedure, or prior stroke within a year were excluded. The adjusted primary outcome was 1‐year stroke events. The adjusted secondary outcomes included bleeding, intracranial hemorrhage, and death. A total of 21 131 patients were included in the study (13 004 TAVR patients were discharged on a vitamin K antagonist and 8127 were discharged on DOACs.) The use of DOACs increased 5.5‐fold from 2013 to 2018. The 1‐year incidence of stroke was comparable between DOAC‐treated patients and vitamin K antagonist‐treated patients (2.51% versus 2.37%; hazard ratio [HR], 1.00; 95% CI, 0.81–1.23) whereas DOAC‐treated patients had lower 1‐year incidence of any bleeding (11.9% versus 15.0%; HR, 0.81; 95% CI, 0.75–0.89), intracranial hemorrhage (0.33% versus 0.59%; HR, 0.54; 95% CI, 0.33–0.87), and death (15.8% versus 18.2%; HR, 0.92; 95% CI, 0.85–1.00). Conclusions In patients with TAVR and atrial fibrillation, DOAC use, when compared with vitamin K antagonists, was associated with comparable stroke risk and significantly lower risks of bleeding, intracranial hemorrhage, and death at 1 year.

Evaluation of the Modified SAMe-TT2R2 Score to Predict Good Anticoagulation Control with Warfarin Among non-valvular Atrial Fibrillation Patients

Background: The SAMe-TT2 R2 Score was developed to identify vitamin K antagonists control outliers before non-valvular atrial fibrillation (AF) patients start treatment. SAMe-TT2 R2 Score was derived and validated using a primarily white Caucasian population to predict TTR. Given that non-Caucasian race already confers 2 points in this score, the SAMe-TT2 R2 score requires validation and/or re-calibration despite race of population. Method: We conducted a cohort retrospective study that included all non-valvular atrial fibrillation patients who were on warfarin therapy from January to December 2019. Then we calculated the modified SAMe-TT2 R2 and SAMe-TT2 R2 for all study populations and we correlated the result with patients' TTR. The TTR was calculated through the Rosendaal's method. Results: We had 662 patient using warfarin therapy, among those 662, 60.9% were under cardiology and using it for cardiac indication, and only 18.1% diagnosed to have non-valvular AF. Modified SAMe-TT2 R2 score has good relation to original SAMe-TT2 R2 score as showed 75.71% (95% CI. 63.99 to 85.17%), 100% (95% CI. 92.89 to 100%) and 15% (95% CI. 3.21 to 77.95%); accuracy, sensitivity and specificity in relation to SAMe-TT2 R2 respectively. In addition to that in this small cohort we found that there is universal relationship between SAMe-TT2 R2 score, Modified SAMe-TT2 R2 score and TTR; TTR >=65% associate with low score (<2) of both SAMe-TT2 R2 , Modified SAMe-TT2 R2 score. Conclusion: The use of Modified SAMe-TT2 R2 score allows clinicians to make an informed decision on whether to start vitamin K antagonist or other non-vitamin K antagonist oral anticoagulant despite the race of the patients.

Anticoagulation Practice in Patients with Cancer-Associated Thrombosis: Insights from GeCAT, a German Prospective Registry Study

Introduction: Cancer-associated venous thrombosis (CAT) is a common and serious complication of active malignancies, increasing in frequency during systemic treatment and radiotherapy. Due to a high risk of recurrence and bleeding, the administration of anticoagulants for initial treatment and secondary prevention of CAT is challenging. We conducted a prospective registry study of patients with acute CAT to evaluate the way treatment is given to these patients in routine practice. Methods: From May 2015 to May 2017, all consecutive patients with acute venous thromboembolism (VTE) admitted to specialty or emergency departments of the participating hospitals in Berlin, Germany, were entered in the registry. Patients with cancer underwent extensive baseline evaluation including the type and location of thrombosis and use of anticoagulant therapy. Follow-up assessments were made at discharge and by telephone interviews at 3 and 6 months. Results: A total of 382 patients with acute CAT were enrolled in the study, representing 24.5% of all patients with thrombosis. 70.4% of CAT patients had deep vein thromboses (DVT), 48.2% had pulmonary embolism (PE), and 18.6% had concurrent PE and DVT. A significant proportion of VTE (27%) were asymptomatic and were diagnosed only incidentally. At baseline, 97.9% of the patients received anticoagulant therapy, predominantly with low-molecular-weight heparin (LMWH) (n=334, 87.4%). Direct oral anticoagulants (DOACs) were given to 5.8% of patients, and vitamin K antagonists (VKAs) were rarely used (<2% of patients). Changes in the prescription of antithrombotic agents were seen at discharge from hospital and during follow-up. Overall, the use of LMWH declined during follow-up, while the proportion of patients treated with DOACs increased to 32.4% at 6 months. At baseline, the most frequently used LMWH were enoxaparin and nadroparin, but many patients were switched to once daily tinzaparin prior to discharge. Initially and after discharge the majority of patients were treated by oncologists. Overall, 263 (68.8%) and 222 (58,1%) patients were still alive and could be contacted at 3 and 6 months of follow-up, respectively. Of these, 84.0% and 71.6% were still on anticoagulant therapy (58.6% and 36.5% on LMWH). Conclusion: In accordance with the guidelines, the majority of CAT patients received anticoagulation therapy for the recommended minimum duration of 3-6 months. LMWH remained the preferred option throughout the study, demonstrating good patient adherence. In deviation from guideline recommendations and available study results during the study period, more than a quarter of CAT patients were treated with DOACs. Only recently, DOACs have been established as another option for anticoagulation in CAT patients.

Direct Oral Anticoagulants and Vitamin K Antagonists: Role in Thrombotic Damage, Safety, and Indications

This chapter is intended to discuss the available oral anticoagulants, including vitamin K antagonists and the Direct Oral Anticoagulants such as dabigatran, apixaban, rivaroxaban, and edoxaban. It will review their basic pharmacology, pharmacokinetics, pharmacodynamics, dosage forms, clinical indications, and place in therapy. Finally, this chapter will also discuss the currently available reversal agents.

Recent Advances in Anticoagulant Treatment of Immune Thrombosis: A Focus on Direct Oral Anticoagulants in Heparin-Induced Thrombocytopenia and Anti-Phospholipid Syndrome

For more than 10 years, direct oral anticoagulants (DOACs) have been increasingly prescribed for the prevention and treatment of thrombotic events. However, their use in immunothrombotic disorders, namely heparin-induced thrombocytopenia (HIT) and antiphospholipid syndrome (APS), is still under investigation. The prothrombotic state resulting from the autoimmune mechanism, multicellular activation, and platelet count decrease, constitutes similarities between HIT and APS. Moreover, they both share the complexity of the biological diagnosis. Current treatment of HIT firstly relies on parenteral non-heparin therapies, but DOACs have been included in American and French guidelines for a few years, providing the advantage of limiting the need for treatment monitoring. In APS, vitamin K antagonists are conversely the main treatment (+/- anti-platelet agents), and the use of DOACs is either subject to precautionary recommendations or is not recommended in severe APS. While some randomized controlled trials have been conducted regarding the use of DOACs in APS, only retrospective studies have examined HIT. In addition, vaccine-induced immune thrombotic thrombocytopenia (VITT) is now a part of immunothrombotic disorders, and guidelines have been created concerning an anticoagulant strategy in this case. This literature review aims to summarize available data on HIT, APS, and VITT treatments and define the use of DOACs in therapeutic strategies.

Safety and differences between direct oral anticoagulants and vitamin K antagonists in the risk of post-traumatic intrathoracic bleeding after rib fractures in elderly patients

Closed chest traumas are frequent consequences of falls in the elderly. The presence of concomitant oral anticoagulant therapy can increase the risk of post-traumatic bleeding even in cases of trauma with non-severe dynamics. There is limited information about the differences between vitamin K antagonists and direct oral anticoagulants in the risk of post-traumatic bleeding. To assess differences in the risk of developing intra-thoracic hemorrhages after chest trauma with at least one rib fracture caused by an accidental fall in patients over 75 years of age taking oral anticoagulant therapy. This study involved data from four emergency departments over two years. All patients on oral anticoagulant therapy and over 75 years of age who reported a closed thoracic trauma with at least one rib fracture were retrospectively evaluated. Patients were divided into two study groups according their anticoagulant therapy. Of the 342 patients included in the study, 38.9% (133/342) were treated with direct oral anticoagulants and 61.1% (209/342) were treated with vitamin K antagonist. A total of 7% (24/342) of patients presented intrathoracic bleeding, while 5% (17/342) required surgery or died as a result for the trauma. Posttraumatic intrathoracic bleeding occurred in 4.5% (6/133) of patients receiving direct oral anticoagulants and 8.6% (18/209) of patients receiving vitamin K antagonist. Logistic regression analysis, revealed no difference in the risk of intrathoracic haemorrhages between the two studied groups. Direct oral anticoagulants therapy presents a risk of post-traumatic intrathoracic haemorrhage comparable to that of vitamin K antagonist therapy.