The purpose of this review is to examine the possibilities and prospects for the use of direct oral anticoagulants for the prevention of thromboembolic complications in patients with atrial fibrillation and chronic kidney disease. Chronic kidney disease is an independent risk factor for cardiovascular complications. Atrial fibrillation is associated with a higher risk of developing chronic kidney disease and more rapid progression of existing renal pathology. The presence of chronic kidney disease in atrial fibrillation on the one hand leads to an increased risk of thromboembolism, and on the other to an increased risk of bleeding when using anticoagulants. The standard for the prevention of thromboembolic complications in atrial fibrillation, including those with concomitant renal pathology, was considered warfarin for many years. However, modern studies have shown that the use of warfarin may enhance vascular calcification in patients with chronic kidney disease, which in turn may lead to an increased risk of ischemic strokes.Analyzing clinical recommendations, randomized studies, meta-analyzes and a systematic review on the use of anticoagulants in patients with atrial fibrillation and renal pathology, revealed the advantage of using direct oral anticoagulants over warfarin at stage 1-3 of chronic kidney disease. Data on the use of direct oral anticoagulants with a more pronounced renal dysfunction and in patients on dialysis is limited due to the lack of a sufficient number of large randomized studies. Due to the presence of renal clearance in all oral anticoagulants, their pharmacokinetics changes to some extent with a decrease in the glomerular filtration rate, which requires dose adjustment of drugs depending on creatinine clearance. Therefore, the use of anticoagulants for the prevention of thromboembolic complications during atrial fibrillation requires special attention in patients with chronic kidney disease.

The search for new drugs providing effective and safe therapy of acid-dependent diseases of the gastrointestinal tract, continues to be an actual problem of modern pharmacotherapy. One of the most significant pathogenetic mechanisms of these diseases is associated with Helicobacter pylori damage to the gastric mucosa.The aim of this study is the experimental investigation of the antiulcer effect of 2-phenyl-9-diethylaminoethylamine [1,2-a] benzimidazole substance (hereinafter a Benzimidazole derivative substance) on the model of Helicobacter pylori-like gastric mucosal injury in combination with immobilization stress (a restraint).Materials and methods. For modeling a mucous membrane damage to experimental animals (white Wistar male rats), they were injected 120 mmol/l ammonia solution after a 24-hour immobilization stress (restraint). As reference drugs, the following officinal anti-ulcer drugs widely used in clinical practice, had been chosen: Rranitidine (30 mg/kg, 10 mg/kg and 3 mg/kg) and Omeprazole (3 mg/kg, 1 mg/kg and 0.3 mg/kg). The study substance was used in the doses of 30 mg/kg, 10 mg/kg and 3 mg/kg. The maximum doses of the reference drugs were calculated on the basis of maximum daily doses for humans, taking into consideration the interspecies conversion factor. The maximum dose of the substance under study was selected experimentally. The logarithmic dose range was used for the convenience of further calculations of the ED50 value. All the studied objects were introduced intragastrically through a non-traumatic tube.Results and discussion. It has been established that the studied substance significantly reduced the area of mucosal damage relative to the control values in modeling Helicobacter pylori-like gastric mucosal injury provoked by the administration of ammonia solution against the background of gastric mucosal ischemia after a 24-hour restraint. At the same time, the inhibition of ulceration reached 78%, while in the groups receiving Ranitidine and Omeprazole, it reached 66% and 50%, respectively. The calculated ED50 values were the following: for the substance under study – 16.03 mg/kg, and for Ranitidine – 15.99 mg/kg.Conclusion. The gained results indicate that the studied Benzimidazole derivative is superior to analogs in its ability to suppress gastric mucosal ulceration provoked by Helicobacter pylori-like gastric mucosal injury, which confirms the relevance of further study of anti-ulcer activity and the development of the pharmaceutical dosage form based on it.

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.

Background. Every fifth ischemic stroke is caused by a patient’s history of atrial fibrillation. Nowadays, direct and indirect oral anticoagulants are widely used to prevent thromboembolic complications in patients with atrial fibrillation. However, despite the prescription of this group of drugs, every year 1–2% of patients with atrial fibrillation have an ischemic stroke. In this situation, a number of questions take rise: if it is possible to carry out thrombolytic therapy in the patients who have been taking anticoagulants; if it is worth resuming anticoagulant therapy after a stroke; when exactly this should be done; and what drugs should be used to prevent another stroke.The aim of this review was to summarize the available clinical guidelines and research results on the study of the anticoagu- lant therapy characteristics in patients with atrial fibrillation after an ischemic stroke.Materials and methods. For this review, the information presented in the scientific literature from open and available sourc- es, has been used. The information had been placed in the following electronic databases: PubMed, Scopus, Web of Sci- ence Core Collection, Cochrane Library, ClinicalTrials.gov; Elibrary, Cyberleninka, Google Academy. The covering period was 1997–2020. The search queries were: “ischemic stroke + atrial fibrillation + anticoagulants”; “ischemic stroke + atrial fibrillation + direct oral coagulants” and “atrial fibrillation + ischemic stroke + warfarin” in both Russian and English equivalents.Results and conclusion. Currently, the problem of the use of anticoagulants for the prevention of recurrent thromboembolic complications in patients with AF in the acute period of a stroke, is studied insufficiently. The difficulties are caused by the delivery of TLT in the patients who have been taking DOACs, first of all, due to the impossibility of an accurate assessment of the hemostasis state because of the unavailability of routine specific tests; and second, as a result of the lack of registered antidotes for most drugs, and their high costs. Besides, there are no RCTs dedicated to the study of the optimal time for the resumption or initiation of anticoagulant therapy in the acute period of an IS, and the optimal drugs for this group of patients. Most of the existing recommendations on these aspects, are based on the consensus of experts, and this fact indicates the need for further research in the area under review.

Aim To compare efficacy and safety of direct oral anticoagulants (DOACs) for prevention of stroke in patients with nonvalvular atrial fibrillation and reduced creatinine clearance.Material and methods Systematic search for literature and indirect comparison of DOACs were performed.Results The indirect comparison included five randomized clinical trials. The DOACs were comparable by the efficacy of preventing stroke and systemic embolism. The safety profiles had differences. Apixaban significantly decreased the relative risk of major bleeding compared to rivaroxaban by 27 % (relative risk (RR) 0.73; 95 % confidence interval (CI): 0.55–0.98). The apixaban advantage was even greater in the group of patients with a creatinine clearance <50 ml/min: RR was reduced by 48 % compared to rivaroxaban (RR=0.52; 95 % CI: 0.32–0.84), by 50 % compared to dabigatran 300 mg/day (RR=0.50; 95 % CI: 0.31–0.81), and by 48 % compared to dabigatran 220 mg/day (RR=0.52; 95 % CI: 0.32–0.85)Conclusion The indirect comparison of DOACs showed that their efficacy was comparable. With respect of safety, apixaban is the preferrable DOAC for patients with atrial fibrillation and creatinine clearance below 50 ml/min.