scholarly journals Direct Oral Anticoagulants (DOAC): Are We Ready for a Pharmacogenetic Approach?

2021 ◽  
Vol 12 (1) ◽  
pp. 17
Author(s):  
Raffaele Palmirotta

Anticoagulants play an important role in reducing complications and mortality associated with thromboembolic disorders, and anticoagulant therapy has been progressively enriched over the last few years with numerous new options [...]

Applied Nano ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 98-117
Author(s):  
Yuri B. G. Patriota ◽  
Luíse L. Chaves ◽  
Evren H. Gocke ◽  
Patricia Severino ◽  
Mônica F. R. Soares ◽  
...  

Heparin-based delivery systems have been explored to improve their therapeutic efficacy and to reduce toxicity for different administration routes. Regardless of the applied drug delivery system (DDS), the evaluation of anticoagulant performance is instrumental for the development of a suitable DDS. The understanding of the range of anticoagulant assays, together with their key applications and limitations, is essential both within the context of scientific research and for clinical usage. This review provides an overview of the current anticoagulant therapy and discusses the advantages and limitations of currently available anticoagulant assays. We also discuss studies involving low-molecular-weight heparin (LMWH)-based nanocarriers with emphasis on their anticoagulation performance. Conventional anticoagulants have been used for decades for the treatment of many diseases. Direct oral anticoagulants have overcome some limitations of heparins and vitamin K antagonists. However, the lack of an accurate laboratory assessment, as well as the lack of a factor “xaban” (Xa) inhibitor reversal agent, remains a major problem associated with these anticoagulants. LMWHs represent anticoagulant agents with noteworthy efficacy and safety, and they have been explored to improve their outcomes with various nanocarriers through several administration routes. The main problems related to LMWHs have been surmounted, and improved efficiency may be achieved through the use of DDSs.


Author(s):  
В. И. Потиевская ◽  
А. А. Ахобеков ◽  
М. Ф. Баллюзек

Рассматривается современное состояние вопроса выбора антикоагулянтной терапии при фибрилляции предсердий (ФП) у онкологических больных. Отмечается, что сложность выбора антикоагулянта при злокачественных новообразованиях (ЗНО) определяется такими факторами, как коморбидные сердечно-сосудистые заболевания, нарушения функции печени и почек, метаболические дисфункции, свойственные, прежде всего, пациентам старшей возрастной группы. Приводятся актуальные данные по оценке риска геморрагических и тромбоэмболических осложнений ФП при ЗНО в аспекте возраста. Обсуждаются возможные причины увеличения риска развития ФП во время и после лечения ЗНО, в том числе и в связи с возраст-ассоциированностью этих патологий. Рассмотрены вопросы выбора антикоагулянтов у пациентов, находящихся на активной противоопухолевой терапии, особенно на препаратах из группы прямых оральных антикоагулянтов (ПОАК). Согласно данным обсервационных исследований, именно ПОАК являются перспективным, относительно безопасным и эффективным выбором для онкологических пациентов с ФП, в связи с чем их применение должно активно изучаться в рандомизированных клинических исследованиях с учетом фактора возраста. Подчеркивается, что подбор схемы антикоагулянтной терапии у пациентов с ФП и ЗНО требует междисциплинарного участия кардиологов и онкологов, а часто и гериатров, чтобы индивидуализировать лечение и предложить наиболее эффективную терапию. The current issue of the choice of anticoagulant therapy of atrial fibrillation (AF) in cancer patients is considered. It is noted that the difficulty of choosing an anticoagulant in malignancies is largely determined by age-related factors, such as comorbid cardiovascular diseases, liver and kidney dysfunction, metabolic disorders common for in elderly patients. Current data on the risk assessment of hemorrhagic and thromboembolic complications of AF in cancer patients in the aspect of age presented. During and after cancer treatment, the risk of developing AF can increase, also in connection with the age-associated pathology. Possible reasons of it are discussed. The choice of different anticoagulants groups in patients treated with anticancer therapy, including direct oral anticoagulants (DOAC) is considered. According to available data from observational studies, it is the DOAC that is a promising, relatively safe and effective choice for cancer patients with AF, and therefore their use should be actively studied in randomized trials, considering the factor of age. It is particularly noted that solving this problem requires the interdisciplinary involvement of cardiologists, oncologists, and sometimes, geriatrics, to individualize treatment for each case and to offer the most effective therapy.


Kardiologiia ◽  
2021 ◽  
Vol 61 (10) ◽  
pp. 81-88
Author(s):  
T. N. Novikova

This review focuses on issues of anticoagulant therapy in patients with atrial fibrillation (AF) associated with chronic kidney disease (CKD). Such patients are at high risk of stroke whereas the choice of an anticoagulant is difficult. A wealth of information about a negative effect of warfarin on the kidney function has accumulated. A need for an alternative therapy to warfarin for patients with stage 3-4 CKD has become imminent. In this regard, rivaroxaban seems to be an appropriate replacement for warfarin in such patients. In randomized, controlled studies that evaluated the efficacy of direct oral anticoagulants in comparison with warfarin, the efficacy and safety profile of a “kidney” dose in moderate disorders of kidney function has been studied only for rivaroxaban. Moreover, both randomized, controlled studies and studies performed in the conditions of clinical practice, have demonstrated a more favorable effect of rivaroxaban on kidney function compared to warfarin. Patients with AF associated with CKD require a comprehensive protection, which, according to results of clinical studies, may be provided by rivaroxaban. 


TH Open ◽  
2019 ◽  
Vol 03 (01) ◽  
pp. e67-e76 ◽  
Author(s):  
Juan López-Núñez ◽  
Ricard Pérez-Andrés ◽  
Pierpaolo Di Micco ◽  
Sebastian Schellong ◽  
Covadonga Gómez-Cuervo ◽  
...  

Background The efficacy and safety of the direct oral anticoagulants (DOACs) in fragile patients (age ≥ 75 years and/or creatinine clearance levels ≤ 50 mL/min and/or body weight ≤ 50kg) with venous thromboembolism (VTE) has not been evaluated. Methods We used the RIETE database to compare the rates of the composite of VTE recurrences or major bleeding during anticoagulation in fragile patients with VTE, according to the use of DOACs or standard anticoagulant therapy. Results From January 2013 to April 2018, 24,701 patients were recruited. Of these, 10,054 (41%) were fragile. Initially, 473 fragile patients (4.7%) received DOACs and 8,577 (85%) low-molecular-weight heparin (LMWH). For long-term therapy, 1,298 patients (13%) received DOACs and 5,038 (50%) vitamin K antagonists (VKAs). Overall, 95 patients developed VTE recurrences and 262 had major bleeding. Patients initially receiving DOACs had a lower rate of the composite outcome (hazard ratio [HR]: 0.32; 95% confidence interval [CI]: 0.08–0.88) than those on LMWH. Patients receiving DOACs for long-term therapy had a nonsignificantly lower rate of the composite outcome (HR: 0.70; 95% CI: 0.46–1.03) than those on VKAs. On multivariable analysis, patients initially receiving DOACs had a nonsignificantly lower risk for the composite outcome (HR: 0.36; 95% CI: 0.11–1.15) than those on LMWH, while those receiving DOACs for long-term therapy had a significantly lower risk (HR: 0.61; 95% CI: 0.41–0.92) than those on VKAs. Conclusions Our data suggest that the use of DOACs may be more effective and safe than standard therapy in fragile patients with VTE, a subgroup of patients where the risk for bleeding is particularly high.


2019 ◽  
Vol 15 (1) ◽  
pp. 49-53
Author(s):  
V. I. Petrov ◽  
O. V. Shatalova ◽  
A. S. Gerasimenko ◽  
V. S. Gorbatenko

Aim. To study the frequency of prescribing antithrombotic agents in patients with non-valvular atrial fibrillation (AF) who were hospitalized in the cardiology department of a multidisciplinary hospital.Material and methods. A retrospective one-time study of medical records of 765 patients with non-valvular AF treated in the cardiology department of a multidisciplinary hospital in 2012 and 2016 was performed.Results. All patients were stratified in three groups depending on the CHA2DS2-VASc score. The frequency of prescribing antithrombotic agents was evaluated in each group. A low risk of thromboembolic complications was found in 1% (n=3) of patients in 2012 and 0.6% (n=3) in 2016. All these patients received antithrombotic agents. CHA2DS2-VASc=1 was found in 6% (n=15) of patients with AF in 2012 and in 3.4% (n=17) in 2016. A significant number of patients in this group received anticoagulant therapy with vitamin K antagonists (warfarin) or with direct oral anticoagulants. A high risk of thromboembolic complications (CHA2DS2-VASc≥2) was found in 93% of patient (n=245) in 2012 and in 96% (n=482) in 2016. Anticoagulant therapy was prescribed in 70.2% (n=172) patients with high risk in 2012 and 80% (n=387) in 2016. However, some patients with high risk of thromboembolic complications did not have the necessary therapy.Conclusion. Positive changes in the structure and frequency of prescribing anticoagulant drugs in patients with AF and a high risk of thromboembolic complications were found during the years studied. 


2021 ◽  
pp. 106-126
Author(s):  
Т. N. Novikova

This review is devoted to the safety issues of anticoagulant therapy prescribed for the prevention of stroke and systemic embolism in patients with atrial fibrillation. Direct oral anticoagulants are considered worldwide in accordance with the guidelines for the diagnosis and treatment of atrial fibrillation as the preferred anticoagulant choice for the prevention of stroke and systemic embolism. Direct oral anticoagulants in comparison with vitamin K antagonists generally have similar efficacy, but different safety profiles, primarily, this concerns the risk of large extracranial and, primarily, gastrointestinal hemorrhages. To minimize the risk of bleeding during therapy with direct oral anticoagulants, an individual approach to the choice of the drug for each individual patient is required after assessing the risk of bleeding, searching for a potential bleeding substrate, correcting existing risk factors and eliminating, if possible, the substrate. When choosing an anticoagulant therapy, special attention should be paid to the most vulnerable categories of patients, such as patients of older age groups and patients with concomitant chronic kidney disease. Among the direct oral anticoagulants registered in the Russian Federation, according to meta-analyzes of key randomized clinical trials and real clinical trials, apixaban has the most optimal benefit: risk ratio in a wide range of patients, including vulnerable populations. Dynamic observation, including regular assessment of renal function, control of clinical blood analysis, erythrocyte and platelet levels, after prescribing an individually selected anticoagulant to the patient, ensures the maximum safety of therapy. Small, so-called, annoying bleeding is not a reason for canceling the anticoagulant, but requires a careful search for the causes of bleeding and their correction.


2018 ◽  
Vol 12 (4) ◽  
pp. 235-244
Author(s):  
Gualtiero Palareti

Venous thromboembolism, a frequent and severe disease, has clinically important early and late complications and a strong tendency to recur. Anticoagulant therapy is the mainstay of treatment, performed by immediate administration of: i) parenteral anticoagulants followed by vitamin K antagonists, either dabigatran or edoxaban, two direct oral anticoagulants (DOACs); or ii) direct rivaroxaban or apixaban, two DOACs that can be used as single-drug approach. Treatment should last no less than 3 months in all patients though how long it should last thereafter is a more complex issue. The risk of recurrence results from several event- or patient-associated factors. Some patients have low risk and may be treated for 3 to 6 months only. Others (the majority) have a high risk of recurrence (approximately 50% in 10 years). Unfortunately, the protective effect of anticoagulation against recurrence is present only during treatment and is lost when therapy is stopped. For this reason, international guidelines recommend that there is no pre-definite period of anticoagulation (e.g. 1 or 2 years, and so on) in patients at high risk and suggest instead indefinite (extended) anticoagulation, provided there is no high risk of bleeding. When the decision is difficult, adjunctive criteria may be adopted, such as male sex and abnormal D-dimer assessed after anticoagulation is stopped, to identify patients at high risk who need indefinite therapy. The use of DOACs, especially at lower doses with a lower risk of bleeding, may make indefinite anticoagulation for patients easier.


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