Репозиторий Университета

© 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved. In the clinical practice a physician quite often is at a loss due to “freedom of choice” granted by availability of direct oral anticoagulants (DOAC). If a patient with nonvalvular atrial fibrillation (AF) has indications for therapy with anticoagulants which DOAC should be preferred? What are benefits for a patient with ischemic heart disease and AF when definite NOAC is chosen and what are risks inherent of this choice? Answers to such questions are given in this paper.

© 2018 Stolichnaya Izdatelskaya Kompaniya. The article presents a clinical observation of the left atrial appendage thrombosis in a 51-year-old female patient with a paroxysmal form of nonvalvular atrial fibrillation which occurred despite long-term anticoagulant therapy with apixaban in a full dose (5 mg b.i.d.), and the patient's management. The patient was admitted with recurrent symptomatic paroxysm for more than 48 hours, because of which, in accordance with the recommendations, transesophageal echocardiography was performed before an emergency rhythm restoration. Thrombus in the left atrial appendage 0.5×1.03 cm in size was detected. It was decided to refrain from the immediate restoration of the rhythm due to the very high risk of thromboembolic complications. In connection with the categorical refusal of the patient from warfarin, it was decided to replace apixaban with another direct oral anticoagulant - dabigatran 150 mg bid for a period of 4 weeks followed by performing a control transesophageal echocardiographic study. As a result, no thrombus was found on control echocardiography. The particularity of this observation is concomitant hypertrophic cardiomyopathy and diabetes mellitus type 1 in this patient..

© 2018 Stolichnaya Izdatelskaya Kompaniya. The choice of anticoagulant therapy in patients with atrial fibrillation (AF) and concomitant diseases - coronary heart disease (CHD), including acute coronary syndrome (ACS) in history, peripheral arterial disease (PAD), is discussed in the article. The overall mortality and incidence of myocardial infarction in patients with CHD and AF is higher than in patients with AF without CHD. Patients with AF and PAD compared to patients with AF without PAD have higher risks both stroke and systemic embolism. The prescription of triple antithrombotic therapy is necessary for patients with a combination of AF and CHD who underwent percutaneous coronary interventions (in ACS or elective surgery). The possibility of prescription and duration, the choice of specific drugs and their doses should be determined individually, based on the risks of ischemic events associated with stenting, the risk of ischemic stroke and bleeding. Use of new oral anticoagulants (NOAC) instead of vitamin K antagonists (eg, warfarin), low doses of NOAC, studied in trials and proven efficacy in the prevention of stroke/systemic embolism, the use of clopidogrel as a drug of choice from the P2Y12 inhibitor group, the use of low doses of acetylsalicylic acid (ASA), the routine administration of drugs from the proton pump inhibitor group is recommended to minimize the risk of bleeding. The data of subanalysis of the ARISTOTEL randomized clinical trial, indicating a high profile of efficacy and safety of apixaban in patients with AF, depending on the presence of CHD, PAD, concomitant use of ASA, are also presented in the article. The benefits of apixaban over warfarin for reducing the risk of stroke/systemic embolism, total mortality and the risk of bleeding in a subgroup of CHD patients are just as obvious as in the general population of the ARISTOTLE study, and in the subgroup of patients without CHD. Treatment with apixaban, both in the subgroup of patients taking ASA, and a subgroup of patients without ASA, is accompanied by a lower risk of strokes and systemic embolism and a lower incidence of major bleeding. The risk of stroke or systemic embolism was similar in patients with AF and PAD randomized to the apixaban group or to the warfarin group, as well as in patients with AF without PAD. Patients with AF and PAD who received apixaban or warfarin had a similar incidence of major bleeding or clinically significant minor bleeding..

© 2018 Kryukov et al. Introduction: Difficulties in non-vitamin K anticoagulant (NOAC) administration in acute stroke can be associated with changes in pharmacokinetic parameters of NOAC such as biotransformation, distribution, and excretion. Therefore, obtaining data on pharmacokinetics of NOAC and factors that affect it may help develop algorithms for personalized use of this drug class in patients with acute cardioembolic stroke. Patients and methods: Pharmacokinetics of apixaban in patients with acute stroke was studied earlier by Kryukov et al. The present study enrolled 17 patients with cardioembolic stroke, who received 5 mg of apixaban. In order to evaluate the pharmacokinetic parameters of apixaban, venous blood samples were collected before taking 5 mg of apixaban (point 0) and 1, 2, 3, 4, 10, and 12 hours after drug intake. Blood samples were centrifuged at 3000 rpm for 15 minutes. Separate plasma was aliquoted in Eppendorf tubes and frozen at —70°C until analysis. High-performance liquid chromatography mass spectrometry analysis was used to determine apixaban plasma concentration. Genotyping was performed by real-time polymerase chain reaction. CYP3A isoenzyme group activity was evaluated by determining urinary concentration of endogenous substrate of the enzyme and its metabolite (6-β-hydroxycortisol to cortisol ratio). Statistical analysis was performed using SPSS Statistics version 20.0. The protocol of this study was reviewed and approved by the ethics committee; patients or their representatives signed an informed consent. Results: ABCB1 (rs1045642 and rs4148738) gene polymorphisms do not affect the pharmacokinetics of apixaban as well as CYP3A5 (rs776746) gene polymorphisms. Apixaban pharmacokinetics in groups with different genotypes did not differ statistically significantly. Correlation analysis showed no statistically significant relationship between pharmacokinetic parameters of apixaban and the metabolic activity of CYP3A. Conclusion: Questions such as depending on genotyping results for apixaban dosing and implementation of express genotyping in clinical practice remain open for NOACs. Large population studies are required to clarify the clinical significance of genotyping for this drug class.