[The new Epoch of Antithrombotic Therapy in the Long-Term Prevention of a non-Cardioembolic Stroke].

This article presents current opinions on the role of antithrombotic therapy in secondary prevention of cardiovascular diseases (CVD) in patients after noncardioembolic stroke or a transient ischemic attack on the background of sinus rhythm. This review analytically analyses evidence-based data on antithrombotic drugs used for this secondary prevention. Despite the fact that acetylsalicylic acid (ASA) is still a "gold standard" for prevention of noncardioembolic stroke, the search for rational combinations of antithrombotic drugs to increase the effectiveness of preventive treatment is relevant. The question whether the rivaroxaban treatment as monotherapy or in combination with ASA is more effective than the ASA monotherapy for secondary prevention of cardiovascular complications (CVC) was addressed in the COMPASS study. In that study, three regimens of antithrombotic therapy were compared in patients with stable atherosclerotic CVD: rivaroxaban (2.5 mg twice a day) in combination with ASA (100 mg/day); rivaroxaban (5 mg twice a day); and ASA (100 mg/day). Risk for development of major CVC (death, stroke, myocardial infarction (IM)) was lower (p<0.001) in the rivaroxaban+ASA combination treatment group than in the ASA monotherapy group; however, the risk of major bleedings was somewhat higher. Total risk based on the definition of "pure clinical benefit" was lower for the rivaroxaban+ASA combination treatment than for the ASA monotherapy. The rivaroxaban monotherapy did not result in a significant decrease in the risk of major CVC compared to the ASA monotherapy but significantly increased the risk of major bleedings. Incidence of repeated ischemic stroke for a year was 1.1% for the combination therapy, 2.6% for the rivaroxaban therapy, and 3.4% for the ASA monotherapy with significant differences between the combination treatment group and the ASA monotherapy group (p<0.01). Relative risk of repeated stroke was 67% lower for the combination therapy group compared to the ASA monotherapy group. The combination of rivaroxaban (2.5 mg twice a day) and ASA (100 mg) opens a new epoch of antithrombotic treatment for primary and secondary prevention of stroke in patients with a stable atherosclerotic CVD and sinus rhythm.

[Prevention of ischemic stroke in atrial fibrillation from the point of view of a neurologist. Standards and real clinical practice].

The article outlines aspects of the current state of the problem of the priority choice of an oral anticoagulant for indefinite prevention of stroke and systemic thromboembolism in patients with atrial fibrillation. The advantages of direct oral angicoagulants over warfarin are presented, as well as a comparative analysis of the individual characteristics of the main direct oral angicoagulants from the point of view of personification of preventive therapy in accordance with modern treatment standards. The efficacy and safety of oral anticoagulant therapy has been reviewed in terms of the net clinical benefit. Particular attention is paid to the age-related aspects of choosing an anticoagulant for indefinite prophylaxis; an assessment of anticoagulants is presented in accordance with the FORTA concept, which regulates the use of drugs in elderly patients. In conclusion, recommendations are formulated for the choice of an anticoagulant in patients with atrial fibrillation in the most common clinical situations. As a general rule, the choice of a particular drug should be individualized based on risk factors, tolerability, net clinical benefit, patient preference, potential adverse interactions, and other clinical characteristics.

[Arterial Hypertension and Optimization of Medication Prevention of Ischemic Stroke].

The article is devoted to the actual problem - the prevention of stroke in patients with arterial hypertension (AH). Mechanisms of cerebral complications of AH, the key areas of prevention of stroke are presented. On the basis of earlier large randomized trials justified the use of fixed combination products (polypills) comprising, along with antihypertensive lipid-lowering drugs, which is the key to improving treatment adherence and effectiveness of pharmacological prevention of stroke.

[Sleep-disordered breathing syndrome in acute ischemic stroke]. / Sindrom narusheniya dykhaniya vo sne pri ishemicheskom insul'te.

AIM: To evaluate the prevalence, structure and risk factors of sleep-disordered breathing in patients with acute ischemic stroke. MATERIAL AND METHODS: This prospective study included 54 acute ischemic stroke patients aged 66 [57; 72] years, 32 men, 22 women. The diagnosis was confirmed by MRI. The neurological state was assessed with the NIHSS and modified Rankin Scale (mRS). To verify the SDB, cardiorespiratory monitoring was performed on 2-5 day from stroke onset. Total number of SDB episodes, apnea/hypopnea index (AHI), the index of hypoxemia (IH) were registered. RESULTS AND CONCLUSION: SDB was detected in 50 (92%) patients, including 44 (88%) with predominantly obstructive apneas (OA), 6 (12%) patients with central apnea (CA). It was found that the severity of respiratory disorders did not depend on the severity of the neurological state but is associated with a variety of somatic, hemodynamic and metabolic disorders (increased BMI, smoking, diabetes mellitus,atrial fibrillation - AF). Cardioembolic stroke (СES) was accompanied by a more pronounced SDB and can be considered as a marker of respiratory disorders during sleep, especially in patients with AF. Involvement of the insula in the brain infarct zone is a significant factor in the development of SDB and increase of central apnea (CA). Multiple small deep (lacunar) infarcts of the brain, including asymptomatic infarcts, visualized by MRI also indicate a high risk of obstructive SDB.

[Prognostic factors of recurrent acute cerebrovascular incidents in patients with ischemic stroke]. / Prognosticheskie faktory razvitiya povtornykh ostrykh narushenii mozgovogo krovoobrashcheniya u bol'nykh s ishemicheskim insul'tom.

OBJECTIVE: To establish prognostic factors of recurrent acute cerebrovascular complications after ischemic stroke. MATERIAL AND METHODS: A prospective observational study on the 21-22nd day of the acute stage of ischemic stroke included 148 patients, aged 60 [5; 68] years. Following the discharge, a unified telephone survey of patients or their relatives was performed every 3 months. Recurrent strokes, including those with fatal outcome, and transient ischemic attacks (TIA) were recorded. RESULTS AND CONCLUSION: The long-term prospective follow-up duration was 35 [28; 40] months. In 26 (18%) patients, 31 cerebral complications, including 24 recurrent ischemic strokes, 6 TIA, 1 hypertensive intracerebral hemorrhage were registered. Recurrent cerebral complications found to be associated with age older 67 years, ischemic heart disease, multiple focal brain lesions, supraventricular arrhythmias more 46/day, bradyarrhythmias, ventricular arrhythmias. The use of thiazide and thiazide-liked diuretics as part of antihypertensive therapy was associated with a reduced risk of cerebral complications.

[Proignostic Factors of Cardiovascular Complications After Ischemic Stroke].

We included into prospective cohort observational study 148 patients with ischemic stroke aged 60 [52; 68] years. Duration of a prospective follow-up was 35 [28; 40] months. Cardiovascular events (CVE) registered during follow-up were recurrent stroke, transient ischemic attack, myocardial infarction, unstable angina, congestive heart failure, including acute decompensation of chronic heart failure requiring hospitalization, cardiovascular death. During follow-up 37 patients (25%) had 50 CVE. On multivariate regression analysis, independent predictors of CVE after ischemic stroke were: age over 67 years, presence of chronic ischemic heart disease, high grade ventricular arrhythmias, standard deviation of cardiointervals (SDNN) less than 71 ms, absence of thiazide diuretics in the basic antihypertensive therapy.

[Prognostic Factors of Cardiovascular Complications After Ischemic Stroke].

We included into prospective cohort observational study 148 patients with ischemic stroke aged 60 [52; 68] years. Duration of a prospective follow-up was 35 [28; 40] months. Cardiovascular events (CVE) registered during follow-up were recurrent stroke, transient ischemic attack, myocardial infarction, unstable angina, congestive heart failure, including acute decompensation of chronic heart failure requiring hospitalization, cardiovascular death. During follow-up 37 patients (25%) had 50 CVE. On multivariate regression analysis, independent predictors of CVE after ischemic stroke were: age over 67 years, presence of chronic ischemic heart disease, high grade ventricular arrhythmias, standard deviation of cardiointervals (SDNN) less than 71 ms, absence of thiazide diuretics in the basic antihypertensive therapy.

[Cardiac complications and heart rhythm variability in the late post-stroke period].

The aim of this prospective study was to elucidate the relationship between cardiac complications and heart rhythm variability (HRV) in 90 patients (age median 58 (53;67) years) with the sinus rhythm after ischemic stroke. 24-hr Holter monitoring 21 days after stroke was used for temporal and spectral analysis of HRV. The follow-up period lasted 23 (12; 45) months. Ten (11%) patients of this group developed acute myocardial infarction, unstable angina, acute cardiac failure or sudden cardiac death. The remaining 80 (89%) patients constituted group 2. The two groups were matched for the duration of prospective observation, sex, ischemic stroke subtype, the size and localization of brain infarction, multiplicity of focal cerebral lesions, severity of neurologic disorders (Rankin scale), the history of myocardial infarction, the presence of diabetes and chronic heart failure. Patients of group 1 were older in the end of the acute stroke period than those of group 2 (68 (61;72) and 57 (51;66) years) respectively. They, more frequently suffered CHD (stable angina) and had lower spectral characteristics of HRV (p < 0.05).

[Cardioneurology: the up-to-date key positions and the future prospects].

The up-to-date key positions and the future prospects of cardioneurology were analyzed. The wide range of questions of cardioneurology was represented and the necessity of the interdisciplinary approach to the diagnostics, treating and prevention of the cerebrovascular diseases were proved. It was pointed that the studied problems are the priority directions in angioneurology and have great social and clinical importance.

[Cardioneurological aspects of antiplatelet therapy in secondary prevention of cardiovascular diseases].

The paper reflects contemporary views of the role of antiplatelet therapy in secondary prevention of cardiovascular diseases in patients with coronary heart disease and ischemic stroke. On the basis of evidence based medicine analytical characteristics of all antiplatelet drugs subjected to clinical trials in the world are presented. Advantages and imperfectness of each agent both as monotherapy and used in combinations are demonstrated. Main principles of selection of antiplatelet drugs in patients after ischemic stroke, myocardial infarction, or in stable manifestations of coronary atherosclerosis are also given.

[Comparative clinical and anatomic characteristic of patients with patent foramen ovale in cryptogenic and noncryptogenic stroke].

In order to study anatomical and functional characteristics of patent foramen ovale (PFO) in patients with cryptogenic stroke and with other stroke subtypes we examined 56 stroke patients (male--35, female--21, age 46.7 +/- 16.5 years) with PFO and ischemic stroke. Diagnosis of PFO was made by transesophageal echocardiography (TEE), contrast transcranial Doppler monitoring (C-TCD), contrast transthoracic echocardiography (C-TTE). Group 1 was made up of patients with definite stroke cause (cardioembolic, lacunar, atherotrombotic) (n=40), and group 2--of patients with cryptogenic stroke (n=16). Patients in group 2 were younger than patients in group 1 (38.7 +/- 13.4 and 50.4 +/- 16.5 years, p < 0.05) and had slight neurological symptoms. These patients also more frequently had avalvular, or "window-like" anatomic types of PFO (2 [13%] and 4 [27%] patients, respectively), combination of large anatomic size (3 mm and larger) and functional level of PFO (3 degree of the right-to-left shunt by C-TCD) (p < 0.05).

[Pathogenetic significance of patent foramen ovale in patients with the determined cause of ischemic insult].

The prevalence of open oval window (OOW) in patients with different types of ischemic insult and the possibility of independent pathogenetic contribution of OOW to brain injury were evaluated by examining 85 patients (mean age 53 +/- 14 yr) with cardioembolic (CES), lacunar (LS), and other subtypes of ischemic insult. CT and MRT of the head, duplex scanning of head arteries, contrast transcranial monitoring middle cerebral arteries, standard and contrast transthoracic and transoesophageal echocardiography revealed OOW in 40% of the patients. It had small anatomic and functional size and a tunnel-like shape. The presence of an interatrial shunt was unrelated to the degree of neurologic deficit, the size and location of brain injuries, the number of ischemic foci. It is concluded that OOW has no pathogenetic significance of its own and makes no contribution to brain injury in stroke-affected patients.

[Cerebral circulation in chronic hypertensive encephalopathy].

Cerebral blood supply was studied in 123 patients with stage III hypertensive encephalopathy (HE) in the absence of occlusion of main head arteries. Duplex scanning was used to measure blood flow rate in common carotid (CCA), vertebral (VA) and medial cerebral (MCA) arteries. Cortical cerebral blood flow (CBF) was measured by single-photon emission CT using 99mTc- ceretec. Normal and stable blood flow in CCA and VA was documented at all HE stages whereas it decreased in MCA of patients with HE II-III. Cortical CBF in frontal and parietal segments in HE II-II was higher than in HE I (p < 0.05). These findings suggest impaired subcortical perfusion and correlation of the discrepancy between cortical and subcortical blood supply with the severity of HE. Leukoaraosis is an indicator of hypoperfusion.

[Paradoxical embolism in patients with ischemic stroke].

The present study included 84 patients with ischemic stroke of known and unknown etiology. The risk of paradoxical embolism (PE) was evaluated using contrast transthoracic echocardiography, contrast transcranial Doppler monitoring, and transoesophagal echocardiography. The majority 64%) of the patients with strokes of known etiology were found to be predisposed to PE because they had the patent interatrial foramen (PIF) and pulmonary shunt (51 and 13 respectively). PIF was of small functional and anatomical size. Predisposition to PE in most patients with cryptogenic stroke (94%) was due to the presence of PIF (in 88%) and was often the sole cause of the stroke. These patients frequently had the shunt of a large functional size.

[Cerebral hemodynamics and endothelium function in patients with cerebrovascular pathology treated by teveten].

Teveten (eprosartan mesilate) was used as a monotherapy or in combination with hypotiazide (12,5 mg/day) in dosage 600 mg once a day for treatment of 20 patients with cerebrovascular pathology (chronic cerebrovascular insufficiency, consequences of brain ischemica in the presence of arterial hypertension stage I-II, or higher borderline levels of normal blood pressure (BP). Treatment duration was 12 weeks, 24-h monitoring of BP was made some indices of cerebral blood flow, hemodynamics and peripheral vessels reaction were registered. Modulating antihypertensive effect of Teveten was found, statistically significant reduction of systolic BP did not result in worsening of cerebral hemodynamics. Moreover, there was an improvement of endothelial function. Therefore, teveten may be recommended for treatment of patients with cerebrovascular pathology both with arterial hypertension and higher borderline BP.

[Cerebral perfusion in patients with arterial hypertension and chronic forms of brain vascular pathology]. / Tserebral'naia perfuziia u bol'nykh arterial'noi gipertoniei i s khronicheskimi formami sosudistoi patologii golovnogo mozga.

AIM: To examine cerebral perfusion in patients with dyscirculatory encephalopathy and residual disorders of cerebral circulation in arterial hypertension. MATERIAL AND METHODS: Duplex scanning of extra- and intracranial arteries, computed tomography of the head were performed in 26 hypertensive patients with chronic vascular pathology of the brain. Cerebral perfusion was studied by the evidence obtained at single-photon emission computed tomography. RESULTS: Impaired segmental perfusion of the brain, primarily of frontal and temporal location, was detected in 88.5% patients. Occlusive lesions of extra- and intracranial arteries were accompanied by significant deterioration of the perfusion while visualization of leukoaraosis was associated with high perfusion in the anterior frontal compartments indirectly pointing to defects in autoregulation of cerebral circulation. It was found that different correlations exist between perfusion of various segments of the brain and systemic arterial pressure. This is explained by functional and hemodynamic heterogenicity of different brain regions. CONCLUSION: Specific features of cerebral perfusion in patients with chronic forms of vascular brain pathology should be considered in planning antihypertensive therapy because of the risk of focal hypoxia and even ischemia in an inadequate fall of arterial pressure.

[Pathogenetic assessment of cardiac arrhythmia and myocardial ischemia in hemodynamic stroke]. / Patogeneticheskaia otsenka narushenii ritma serdtsa i ishemii miokarda pri gemodinamicheskom insul'te.

330 patients with ischemic stroke entered the trial. They were divided into two groups: 72 (21.8%) patients with hemodynamic stroke (group 1) and the rest 258 (78.2%) patients with other pathogenetic subtypes of stroke (group 2). Heart rhythm and myocardial ischemia were studied using ECG and Holter monitoring. Electrocardiographically, hemodynamic stroke is characterized by frequent ventricular extrasystole, sick sinus syndrome and transient atrioventricular block of the second and third degree with pauses 2 s and longer, ventricular fibrillation and painless myocardial ischemia. Perpetual and paroxysmal atrial fibrillation and paroxysmal ventricular tachycardia are not pathognomonic for hemodynamic stroke though these disorders can be also considered as independent pathogenetic factors of hemodynamic cerebral focal lesion.

[Echocardiographic changes associated with risk of developing embolic complications in patients with ischemic stroke]. / Ekhokardiograficheskie izmeneniia, sopriazhennye s riskom razvitiia émbolicheskikh oslozhnenii, u bol'nykh s ishemicheskim insul'tom.

AIM: To study echocardiographic parameters associated with embolic complications in patients with cardioembolic and other pathogenetic subtypes of ischemic stroke. MATERIAL AND METHODS: 330 patients with ischemic stroke (IS) were examined. Transthoracal echocardiography was made in all the patients, transesophageal echocardiography was performed in 53 (16.1%) patients. The patients were divided into two groups: 104 (31.5%) patients who survived cardiocerebral embolism (group 1), 226 (68.5%) patients with other pathogenetic subtypes of stroke (group 2). RESULTS: Cardiac pathology was detected in 220 of 330 (66.7%) examinees with ischemic heart disease in 50.0% and 51.3% patients of group 1 and 2, respectively; infectious-inflammatory diseases--in 27.9 and 4.4%, respectively (p < 0.0001), other diseases (mitral prolapse, aneurysm and interatrial defect, idiopathic arhythmia) in 25.0 and 5.3% patients, respectively (p < 0.0001). Left atrial myxoma was diagnosed in 1.9% patients of group 1. CONCLUSION: Echocardiographic changes associated with a risk of embolic complications were visualized in all pathogenetic subtypes of ischemic stroke. In cardioembolic stroke echocardiography detected most frequently prolapse with myxomatous degeneration of the cusps and mitral vegetations, mitral failure, calcinosis of the mitral ring, local hypokinesia of the left ventricle, dilation and thrombosis of the left atrium. Rare changes, indicating cerebral embolism, include replaced aortic and mitral valves, mitral stenosis, cardiac tumor, aneurysm and defect of the interatrial septum.

[Comparative assessment of persistent and paroxysmal atrial fibrillation as causes of cardiocerebral embolism]. / Sravnitel'naia otsenka postoiannoi i paroksizmal'noi fibrilliatsii predserdii v patogeneze kardiotserebral'noi émbolii.

In 66 patients with embolic stroke of cardiac origin (33 with persistent and 33 with paroxysmal atrial fibrillation) transthoracic and transesophageal (21 patients, 31.2%) echocardiography was used for detection of atrial thrombosis. Lone atrial fibrillation was significantly more frequent among patients with paroxysmal atrial fibrillation. Frequency of thrombosis of left atrial appendage was similar in patients with nonrheumatic persistent and paroxysmal atrial fibrillation.