ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ LYUBERTSY STUDY ON MORTALITY RATE IN PATIENTS AFTER CEREBRAL STROKE OR TRANSIENT ISCHEMIC ATTACK ( LIS-2 ) . DESIGN AND MEDICAL TREATMENT ESTIMATION

S.A. Boytsov1, S.Yu. Martsevich1*, M.L. Ginzburg2, N.P. Kutishenko1, L.Yu. Drozdova1, A.V. Akimova1, A.Yu. Suvorov1, M.M. Loukianov1, N.A. Dmitrieva1, O.V.Lerman1, N.Yu. Zhuravskaya1, E.V. Daniels2, A.V. Fokina2, V.N. Yudaev3, V.P. Smirnov2, A.M. Kalinina1, S.V. Kotov4, L.V. Stahovskaya5 1State Research Centre for Preventive Medicine. Petroverigsky per. 10, Moscow, 101990 Russia 2Lyubertsy Regional Hospital No2. Oktyabr’skiy prospect 338, Moscow Region, Lyubertsy, 140006 Russia 3Public Health Department of Lyubertsy District. Zvukovaya ul. 4, Lyubertsy, Moscow Region, 4140000 Russia 4Moscow Regional Research Clinical Institute named after M.F. Vladimirsky. Schepkina ul. 61/2, Moscow, 129110 Russia 5Pirogov Russian National Research Medical University. Ostrovitianova ul. 1, Moscow, 1117997 Russia


Authors' information:
Sergey A. Boytsov  Cerebral stroke is the leading cause of mortality in majority of developed countries [1].Patients survived acute period of stroke are at high risk of recurrent stroke occurrence and have a rather poor life prognosis [2,3].However, evidence-based data clearly testify that some concrete medical preparations can significantly improve this prognosis [4].
Cerebral stroke risk factors are in general coincide with other cardiovascular diseases risk factors, first of all with those of ischemic heart disease (IHD).Stroke pathogenesis, especially of its most prevalent type -ischemic stroke (cerebral infarction) due to atherothrombosis, is similar to that one of myocardial infarction (MI) [5,6].
This apparently determines similarity of approaches to the primary and secondary stroke and IHD prevention.It is not surprising that the principal drug groups that have demonstrated their effectiveness in the secondary stroke prevention are to a great extent coincide with medications used for the secondary IHD prevention.First of all these drugs are antiplatelet, antihypertensive and hypolipidemic agents.
Все это, по-видимому, определяет близость подходов к первичной и вторичной профилактике МИ и ИБС.Неудивительно, что основные группы лекарственных препаратов, доказавших свою роль при вторичной профилактике МИ, в значительной степени совпадают с лекарственными препаратами, использующимися для вторичной профилактики ИБС.К этим препаратам, в первую очередь, относятся ан-Pharmacotherapy of patients experienced stroke according to the LIS study data Лекарственная терапия больных, перенесших инсульт, по данным исследования ЛИС-2 Different clinical guidelines present the basic principles for primary and secondary stroke prevention; among them the guidelines promulgated conjointly by the American Heart Association and American Stroke Association are of special interest [7,8].It is well known that the real clinical practice does not always follow modern clinical guidelines.For example, the large-scale international epidemiological study PURE revealed that majority of patients survived stroke do not receive therapy that could really extend their life [9].Respectively, life prognosis of patients in conditions of the real clinical practice can significantly differ from the one registered in large-scale controlled trials.
All these impose a necessity of evaluation of real stroke patients care situation, determination of their life prognosis in conditions of such treatment as well as main factors affecting it.Development of a register, providing evaluation of received treatment quality and patients survival rate during more or less long time period, is known to be the best way of overcoming this problem.
There were a number of cerebral stroke registers established in our country, however, almost all of them were organized in accordance with similar protocol and were aimed at evaluation of stroke morbidity, its risk factors and in-hospital mortality [10][11][12][13][14].Not numerous efforts to estimate long-term outcomes of a treatment were non-systemized and did not meet the requirements of modern research in survival rate evaluation [13].Estimation of risk factors influencing mortality rate was not performed within a framework of the above mentioned registers.
The main aim of our cerebral stroke register, which was called LIS-2 (study of mortality among patients survived cerebral stroke in Lyubertsy district), was the assessment of actual therapy received by the patients and its influence on long-term disease outcomes.This publication presents the design of the study, characteristics of the patients enrolled into it and the treatment prescribed before the reference stroke during hospitalization and after discharge.

Material and methods
The LIS-2 study is a register of patients admitted to the Lyubertsy regional hospital №2 (LRH №2) for cerebral stroke or transient ischemic attack (TIA) from 01.01.2009 to 31.12.2011.
All the consecutive patients admitted to the LRH №2 for stroke (ischemic or hemorrhagic) or TIA from 01.01.2009 to 31.12.2011 were enrolled into the register.Those in whom diagnosis of stroke or TIA at admission was not confirmed were not included.тиагреганты, антигипертензивные и гиполипидемические средства.

Pharmacotherapy of patients experienced stroke according to the LIS study data Лекарственная терапия больных, перенесших инсульт, по данным исследования ЛИС-2
Stroke was diagnosed on the grounds of typical clinical features and specific neurological signs.Such methods of the brain visualization as computer tomography (CT) and magnetic resonance imaging (MRI) were carried out in singular cases in 2009-2010 due to technical capability of the hospital.The patients were examined in accordance with the current health economic standards of medical care.A stroke, a patient was admitted for, was regarded as the reference stroke.Data received at case history analysis concerning patient's history and status at hospitalization, treatment tactics and medications prescribed at discharge from hospital were filled in a special standardized chart and then in an electronic database.
Prospective part of the study designated for discharged patients consisted of several stages.At the first stage telephone contact with a patient or his relatives was obtained, in cases of lethal outcome after the discharge from hospital the cause of death was determined as precisely as possible.At the second stage patients were invited for the control examination, laboratory assays (blood count, lipid profile analysis, ECG) and questionnaires completion.If a patient was not able to attend a doctor by himself, a general practitioner visited him at home, registered ECG and lipid profile indices by a rapid test method using the Car-dioCheck analyzer; all received data were filled in the standardized chart and the electronic database.
This article presents analyzed data from medical records of the patients admitted to hospital from 01.01.2009 to 31.12.2010.
Mean age was 71.0±9.6 years old, youngest age was 25 and oldest 99 years (Fig. 1).It is important to note that primarily patients above 60 years old were hospitalized due to stroke in 2009-2010.567 (89.0%) patients were retirees and 207 (32.5%) were disabled.

Discussion
The LIS-2 register is a limited register, key factor of which is the diagnosis of stroke or TIA in patients admitted to a neurology unit of the municipal hospital.This register has a number of limitations due to difficulties in diagnosis verification, because such methods as CT or MRI were used in singular cases; besides, patients with stroke or TIA predominantly admitted to the hospital were of elderly age (above 60 years old).Due to difficulties in diagnosis verification and taking into account similar approach to primary and secondary stroke and TIA prevention we included in the register both patients with diagnosis of TIA and stroke.
A lot of publications and discussions are devoted to the problem of implementation of evidencebased recommendations in the real clinical practice [15][16][17].Primarily the problem is of current interest in terms of secondary stroke prevention, what has been demonstrated in a number of trials including the above mentioned international epidemiological PURE study [9].
The reasons for this are various and include clinical inertness, presence of controversial data, incompatibility of clinical guidelines made for different nosologies [17][18].Perhaps, in case of stroke, one of such reasons is absence of evident clinical effect of drugs which proved their positive effect on patients life prognosis.
We only estimated drugs prescription in hospital and at the discharge according to nothing else but medical documentation data.In the following actual medical treatment of the survived patients is to be assessed with the help of special questionnaires at repeated visits, what will provide significantly more objective estimation of the treatment quality.
There is one more problem of implementation of evidence-based recommendations in the clinical practice.As is known, randomized controlled trials (RCT), on which recent clinical guidelines are based, are carried out on accurately selected groups of patients.Such patients not always conform to typical patients with variety of concomitant diseases and often extremely older (these patients are oftentimes excluded from studies).So, it is disputable if drugs that have proven their positive effect in RCT would similarly act in the real practice.Modern registers technically allow estimation of drugs influence on disease outcomes, as it was demonstrated in the similar by its design LIS study that included patients survived myocardial infarction [19][20][21].We hope that the LIS-2 study will also let estimate effect of some preparations on long-term outcomes of the disease.

Conclusion
So, the register of patients with cerebral stroke was created in Lyubertsy district (Moscow Region).The results of the register showed that drug therapy used in secondary prevention of cerebral stroke does not well conform to current clinical guidelines.Monitoring of the disease long-term outcomes in the register will identify the key factors that determine long-term prognosis for life and in particular the role of drug therapy.