How to prevent ischemic stroke?

Screening

For the prevention of ischemic stroke, the screening of risk factors and pathological conditions leading to the development of acute focal ischemia and cerebral infarction is of practical importance.

Given the close relationship of obstructive lesions of brachiocephalic arteries with the development of ischemic stroke and the widespread development of surgical methods for the prevention of cerebral circulation, a promising trend is the use of ultrasound diagnostic methods to screen lesions of brachiocephalic arteries followed by a set of preventive measures, including surgical methods. Usually, screening of obstructive lesions of brachiocephalic arteries is performed for individuals over 40 years 1-2 times a year. Screening for heart disease, in particular atrial fibrillation, is also recognized as an important goal in preventing ischemic stroke.

Primary prevention of ischemic stroke

The main goal of the stroke prevention system is to reduce the overall morbidity and reduce the frequency of deaths. Measures aimed at primary prevention of stroke are based on the population social strategy of prevention of cerebrovascular diseases at the state level (mass strategy) and medical prevention (high risk strategy).

A massive strategy is to achieve positive changes in each person in the general population through exposure to modifiable risk factors. The high-risk strategy provides early detection of patients from high-risk groups for the development of a stroke (for example, with arterial hypertension or hemodynamically significant stenosis of the internal carotid artery) followed by a preventive medication and (if necessary) vascular surgery that reduces the incidence of stroke by 50%. Prevention of stroke should be individual and include non-drug measures, targeted medical or angiosurgical treatment.

Efforts to improve the nation are determined by four main strategies: the development of national policies, the strengthening of organizational and human resources, the dissemination of information and training of primary care physicians.

Mass (population) strategy is aimed at informing the population about the modified risk factors associated with lifestyle, and the possibility of their correction. The structure of preventive measures includes informing the population about risk factors through the mass media and issuing special leaflets and posters, as well as medical examination of the population in accordance with the algorithm of primary prevention. According to this algorithm, according to the results of examination and consultation of narrow specialists, patients are referred to different dispensary groups:

• group A - practically healthy (repeated examination in 2-3 years);
• group B - persons with risk factors for cardiovascular disease, but without clinical manifestations of neurological disorders, and patients who had carotid noise in the auscultation of the neck vessels;
• group B - patients with risk factors for cardiovascular disease and clinical manifestations of neurological disorders.

Thus, according to the results of the survey, a contingent of patients most susceptible to the development of cerebrovascular diseases is identified, a high-risk category, groups B and B.

Patients at high risk groups (B and C) with lifestyle-related risk factors should be given recommendations aimed at maintaining a healthy lifestyle: quitting smoking, reducing alcohol consumption. Eating healthy food and diet, increasing physical activity, maintaining a body mass index of less than 25 kg / m ^2, or reducing body weight by 5-10% of the original.

Normalization of blood pressure can reduce the risk of stroke by 40%, the target level of pressure should be below 140/90 mm Hg, with a particularly important level of diastolic pressure.

When diabetes is important to maintain the optimal concentration of glucose in the blood.

Patients with atrial fibrillation are prescribed anticoagulants (usually warfarin) or antiplatelet agents (acetylsalicylic acid).

With stenosis of carotid arteries by more than 60%, including asymptomatic, consider the possibility of endarterectomy taking into account the age of patients and the risk of postoperative complications. In recent years, angioplasty of vessels (stenting) has been used.

It should be noted the importance of quitting or significantly reducing the number of smoked cigarettes, since the risk of stroke is 1-6 times higher in smokers than in non-smokers. During the first year after quitting smoking, the risk of ischemic stroke decreases by 50%, and after 2-5 years it returns to the level of risk in non-smokers.

The protective effect of physical activity is partially associated with a decrease in body weight and blood pressure, as well as its role in reducing the fibrinogen content and increasing the fibrinolytic activity of tissue plasminogen activator in blood plasma, high-density lipoprotein concentration and glucose tolerance.

All patients should be advised to reduce consumption of table salt, increase consumption of fruits and vegetables and at least 2 times a week to eat fish. In people who eat fatty fish and salmon 2-4 times a week, the risk of stroke is reduced by 48% compared to those who include fish in their diet only once a week.

Over the past 5 years, several programs have been launched aimed at the primary prevention of vascular diseases: a program to combat hypertension, a national program for integrated prevention of noncommunicable diseases (CINDI), a program for the prophylactic examination of the working-age population, with the allocation of risk groups and prevention. The introduction of primary prevention can prevent at least 150 cases of stroke per 100 000 population in 3-5 years.

Secondary prevention of ischemic stroke

It is now established that in patients who survived a stroke, the probability of developing a recurrent cerebral circulation disorder reaches 30%, which is 9 times greater than that in the general population. It is shown that the total risk of recurrent cerebrovascular accident in the first 2 years after the stroke is 4-14%, and in the first month, a second ischemic stroke develops in 2-3% of survivors, in the first year - at 10-16%, then - about 5% per year. The frequency of recurrent stroke during the first year is different for different clinical variants of cerebral infarction: with total carotid infarction it is 6%, in lacunar infarction - 9%, with partial carotid infarction - 17%, with infarct in vertebrobasilar basin - 20% . Similarly, individuals who have undergone transient ischemic attacks are also at risk. In the first year after them, the absolute risk of stroke is about 12% for population studies and 7% for hospital series, the relative risk is 12 times higher than for patients of the same age and sex without transient ischemic attack.

It is shown that individualized secondary prevention of stroke reduces the risk of repeated violation of cerebral circulation by 28-30%. In general, the economic costs of stroke prevention are much less than the costs required for treatment and medical and social rehabilitation of stroke patients, as well as their disability pension. The data show how important it is to develop an adequate system that prevents repeated cerebrovascular disorders.

The data of numerous international studies and systematic reviews demonstrate, as a rule, the effectiveness of one of the directions of secondary prevention of stroke, while the greatest result can be achieved by using a set of preventive measures. The comprehensive program of secondary prevention of stroke is based on the principles of evidence-based medicine and the polytherapy approach. It includes 4 directions: antihypertensive (diuretics, angiotensin converting enzyme inhibitors), antithrombotic (antiaggregants, indirect anticoagulants), lipid-lowering therapy (statins), as well as surgical treatment for stenoses of carotid arteries (carotid endarterectomy).

Thus, to date, the following approaches to secondary prevention of stroke have been identified:

• individual choice of the program of preventive measures depending on risk factors, type and clinical variant of the transferred stroke, concomitant diseases;
• a combination of different therapeutic effects;
• continuity and duration of preventive treatment.

The goal of secondary prevention of cerebral stroke, based on the individual approach of therapeutic measures, is to reduce the risk of recurrent cerebral stroke and other vascular pathology (eg, myocardial infarction, peripheral vascular thrombosis, pulmonary embolism, etc.), and prolong the life of patients. Direct direct criteria for evaluating the effectiveness of therapeutic interventions include reducing the incidence of stroke and prolonging life.

The criteria that determine the choice of strategies for secondary prevention of cerebral stroke are as follows:

• risk factors for stroke;
• pathogenetic type of stroke, both present and previous;
• results of instrumental and laboratory examination, including assessment of the condition of the main arteries of the head and intracerebral vessels, cardiovascular system, rheological properties of blood and hemostasis;
• concomitant diseases and their therapy;
• safety, individual tolerance and contraindications to the use of a particular drug.

Individual secondary prevention of stroke should begin in a hospital from the 2nd to 3rd day of the disease. If secondary prevention was not recommended in the hospital or the patient was on treatment at home, the choice of therapy is performed by the neurologist at the polyclinic on the basis of an additional examination (if not already done), including an ECG, Holter monitoring if necessary (to avoid transient rhythm disturbances and identify atrial arrhythmias), as well as ultrasonic methods (for determining the degree of stenosis of the main arteries of the head) and the study of the lipid spectrum of the blood (to determine hyperlipids emmy). The patient is monitored after the selection of therapy in a clinic by a general practitioner with a frequency of 1 every 3 months during the first year, and subsequently every six months. During visits, assess the patient's condition and analyze everything that has happened since the last visit (vascular disorders, hospitalizations, side effects).

Antihypertensive therapy

Elevated blood pressure is the most important risk factor for developing cerebral stroke. A meta-analysis of the results of 4 randomized clinical trials in which the efficacy of diuretics and beta-adrenoblocker atenolol in arterial hypertension was studied in stroke patients, regardless of blood pressure, revealed an unreliable decrease in the rate of recurrent cerebral circulation impairment by 19%, ie, only a trend towards more rare development of a second stroke on the background of lowering blood pressure.

It has been proved that today the most effective of all antihypertensive drugs are prevention of repeated disorders of cerebral circulation, inhibitor of angiotensin-converting enzyme perindopril and blocker of angiotesin II receptor eprosartan.

Speaking about hypotensive therapy as a secondary prevention of stroke, it should be remembered that it is not just about lowering blood pressure to the target level in patients with hypertension, but also about therapy that prevents further remodeling and hypertrophy of the vascular wall, the progression of atherosclerotic damage, including number in patients with normal blood pressure.

Recommendations

• The drugs of choice for secondary prevention of recurrent cerebral circulation disorders should be considered antihypertensive drugs from the group of angiotensin converting enzyme inhibitors and angiotensin-renin receptor blockers (level of evidence I).
• Angiotensin converting enzyme inhibitors and angiotensin receptor blockers reduce the frequency of recurrent cerebral circulation disorders not only in hypertensive patients but also in normotonics due to the additional angiotoprotective, anti-atherogenic and organoprotective properties of these drugs (level of evidence I).
• Despite the lack of convincing evidence, patients who are at risk for developing hemodynamic stroke due to occlusive or severe stenosis of the carotid arteries or arteries of the vertebrobasilar basin should not excessively reduce blood pressure (level of evidence II).
• Non-medicamentous effects on hypertension should include smoking cessation, limiting intake of table salt, reducing excess body weight, optimizing physical activity, limiting alcohol consumption, reducing the effects of chronic stress, which in themselves can lead to increased blood pressure (level of evidence: II) .

[1], [2], [3], [4], [5], [6], [7],

Antithrombotic therapy

Antithrombotic therapy includes the appointment of antiaggregant and anti-coagulant drugs.

[8], [9], [10], [11], [12], [13]

Antiaggregant therapy

An important role in the pathogenesis of acute disorders of cerebral circulation is attributed to atherothrombosis and changes in the rheological properties of blood, including an increase in the aggregation capacity of platelets and red blood cells. The increased aggregation activity of platelets and massive formation of thromboxane A ₂, detected during atherothrombosis of the main vessels of the head, can be considered adequate markers of hemostatic activation, characteristic for both thrombus formation and atherogenesis. In the residual period of the stroke, the reduction in the atrombogenic reserve of the vascular endothelium (i.e., acute cerebrovascular accident) increases, exerting a significant influence on the haemostatic potential of the blood and the cerebral vascular system, which can exacerbate the process of depletion of the atrombogenic potential of the vascular system, thereby contributing to the progression of atherothrombosis.

A systematic review of antiplatelet studies gave clear evidence of the benefits of antithrombotic therapy: prolonged use of antiplatelet agents reduces the risk of serious vascular events (eg, myocardial infarction, stroke, vascular death) by 25%. Studies evaluating antithrombotic therapy in patients who have a history of stroke or transient ischemic attack have shown that this therapy reduces the 3-year risk of serious vascular episodes from 22 to 18%, which is equivalent to preventing 40 cases of serious vascular episodes in 1000 treated patients ie it is necessary to treat 25 people from the high-risk group for 3 years to avoid one vascular episode with antiplatelet drugs).

The advantages of antithrombotic therapy are proven in various multicenter studies. A meta-analysis of data from randomized trials that examined how effectively various antiplatelet agents and their combinations prevent the development of recurrent cerebral circulation disorders showed that they have approximately the same preventive effect. The spectrum of drugs with antiaggregant effect is quite wide, which allows each patient to choose the optimal therapeutic agent, taking into account individual features of central and cerebral hemodynamics, vascular reactivity, and the state of the vascular wall. When selecting patients, it is necessary to take into account the risk factors for the development of a second stroke in a particular patient (presence of arterial hypertension, diabetes, cardiac pathology, etc.) and the results of the examination using additional methods. Since the effects of the antithrombotic agents used are not significantly different, the basis for the choice of the drug should lie in its safety, the absence of side effects, and also the peculiarities of hemostasis in a particular patient.

To date, in the prevention of repeated disorders of cerebral circulation, the effectiveness of acetylsalicylic acid, dipyridamole and clopidogrel has been most studied.

• Acetylsalicylic acid is the most widely used drug among anti-aggregants. The main mechanism of action of acetylsalicylic acid is the inactivation of the enzyme cyclooxygenase, as a result of which the synthesis of prostaglandins, prostacyclones is disrupted and there is an irreversible disruption of the formation of thromboxane A ₂ in platelets. The drug is prescribed in a dose of 75-100 mg / day (1 μ / kg), released with a special enteric-soluble coating or as a combined preparation with an antacid component.
• Dipyridamole, which belongs to pyrimidine derivatives and which mainly has antiplatelet and vascular action, is the second drug used for secondary prevention of stroke. Dipyridamole is a competitive inhibitor of adenosine deaminase and adenyl phosphodiesterase, which increases adenosine and cAMP in platelets and smooth muscle cells of the vascular wall, preventing inactivation of these substances. Dipiridamole is prescribed in a dose of 75-225 mg / day.
• Clopidogrel is a selective noncompetitive platelet receptor antagonist against ADP, which has an antithrombotic effect due to direct irreversible inhibition of ADP binding to its receptors and subsequent prevention of activation of the GP IIb / IIIa complex.

Recommendations

• To prevent recurrence of cerebral circulation, adequate antiplatelet therapy should be used (level of evidence: I).
• Acetylsalicylic acid in a dose of 100 mg effectively reduces the risk of repeated cerebral strokes (level of evidence I). The frequency of gastrointestinal bleeding during therapy with acetylsalicylic acid is dose-dependent, low doses of the drug are safe (level of evidence I).
• Dipiridamole in a dose of 75-225 mg / day along with acetylsalicylic acid is effective against secondary prevention of ischemic disorders (level of evidence I). It can be a drug of choice in patients with acetylsalicylic acid intolerance (level of evidence II).
• The combination of acetylsalicylic acid (50 mg) and sustained release dipyridamole (150 mg) is more effective than the intake of acetylsalicylic acid alone, preventing recurrent cerebral circulation (level of evidence I). This combination can be recommended as a therapy of choice (level of evidence I).
• Clopidogrel (Plavike) at a dose of 75 mg / day is significantly more effective than acetylsalicylic acid for the prevention of vascular disorders (level of evidence I). It can be prescribed as the first drug of choice for patients with intolerance to acetylsalicylic acid and dipyridamole (level of evidence IV), as well as to patients at high risk (with ischemic heart disease and / or atherothrombotic peripheral arterial disease, diabetes mellitus) (level of evidence II).
• The combination of acetylsalicylic acid (50 mg) and clopidogrel (75 mg) is more effective than monotherapy with these drugs, prevents a second stroke. However, the risk of life-threatening hemorrhages is two times higher than that of monotherapy with clopidogrel or acetylsalicylic acid (level of evidence I).
• Patients who do not have cardiac embolism and who underwent a second stroke with acetylsalicylic acid, the use of anticoagulants (warfarin) does not benefit (level of evidence I).

[14], [15], [16], [17], [18],

Anticoagulant therapy

The cause of every sixth ischemic stroke is thromboembolism from the cavities of the heart. Atrial fibrillation is the main cause of thromboembolic strokes, the risk of recurrence of cerebral circulation is 12% per year. For long-term secondary prevention after the transient ischemic attack and ischemic stroke in patients with atrial fibrillation, antithrombotic drugs are used. In this case, the choice of indirect anticoagulant warfarin becomes indirect, which has shown its effectiveness in the primary prevention of vascular disorders in patients with a high risk of thromboembolic complications. Several large randomized clinical trials have been conducted that determined the tactics of antithrombotic therapy in patients with atrial fibrillation who underwent ischemic stroke and who demonstrated the superiority of anticoagulants to acetylsalicylic acid.

Recommendations

• Warfarin is an effective drug for the prevention of recurrent cerebral circulation disorders in patients with non-valvular atrial fibrillation (level of evidence I).
• The target values of the international normalized relationship, ensuring reliable prevention of ischemic manifestations, correspond to 2.0-3.0 (level of evidence I). High rates of mortality and serious bleeding were noted in patients with excessive hypocoagulation (international normalized ratio> 3.0) (level of evidence I).
• At present, there is no conclusive evidence of the effectiveness of warfarin in the prevention of noncardiogenic ischemic strokes (level of evidence I).

[19], [20], [21], [22],

Lipid-lowering therapy

High blood cholesterol is a significant risk factor for the development of atherosclerosis and its ischemic complications. Lipid-lowering drugs have proven themselves in cardiac practice as a means of primary and secondary prevention of myocardial infarction. However, the role of statins in the prevention of stroke is not so unambiguous. Unlike acute coronary episodes, where the main cause of myocardial infarction is coronary atherosclerosis, atherosclerosis of a large artery causes a stroke in less than half of cases. In addition, there was no clear correlation between the incidence of stroke and the cholesterol level in the blood.

Nevertheless, in a number of randomized clinical studies on primary and secondary prophylaxis of coronary heart disease, it has been shown that therapy with lipid-lowering drugs, namely, statins, reduces the incidence of not only coronary disorders but also cerebral stroke. Analysis of the 4 largest studies examining how effective lipid-lowering therapy is for secondary prevention of coronary heart disease has shown that under the influence of statin therapy, the total stroke rate decreases. Thus, in the 4S study, 70 strokes occurred in the group of patients who received simvastatin 40 mg on average about 4-5 years, and 98 in the placebo group. At the same time, the content of low-density lipoprotein cholesterol decreased by 36%.

Pravastatin in a dose of 40 mg / day showed its effectiveness in a randomized clinical trial of PROSPER (The PROspective Study of Pravastatin in the Elderly at Risk). The drug significantly reduced the risk of coronary mortality and myocardial infarction rate, the risk of developing recurrent cerebral circulatory disorders decreased by 31%, although the frequency of fatal strokes did not change. Pravastatin effectively prevented cerebrovascular disorders in patients over 60 years old without hypertension and diabetes, with an ejection fraction of more than 40%, and in patients with acute cerebrovascular accident in a history.

It should be noted that all the data on which the use of statins for the prevention of cerebral strokes is based is derived from studies whose main goal was to detect a decrease in the incidence of coronary episodes. At the same time, as a rule, they analyzed how the statin therapy affects the total stroke frequency, without taking into account the anamnestic data on whether the stroke was primary or repeated.

Recommendations

• Patients who undergo transient ischemic attack and ischemic stroke in the presence of coronary heart disease, atherothrombotic peripheral arterial disease, diabetes mellitus should receive treatment, including lifestyle changes, dietary nutrition and drug therapy (Level II evidence).
• It is recommended to maintain the target low-density lipoprotein cholesterol content in ischemic heart disease or atherothrombotic lesions of lower limb arteries below 100 mg / dL; in very high-risk individuals with multiple risk factors - below 70 mg / dl (level of evidence: I).
• Statin therapy can be initiated within the first 6 months after a stroke (level of evidence II).
• At present, there is no convincing evidence of the need for statin use in the acute period of cerebral stroke (level of evidence I).
• The use of statins in patients who have suffered a hemorrhagic stroke requires special care. The decision of a question on such treatment accepts taking into account all risk factors and accompanying diseases (a level of proof II).

Carotid endarterectomy

In recent years, convincing data on the advantages of the surgical method of treatment - carotid endarterectomy - have been obtained in comparison with conservative treatment in patients with hemodynamically significant narrowing of the carotid arteries (more than 70% of the lumen of the vessel). In randomized clinical trials, it is shown that the risk of developing cerebral stroke during surgical interventions is reduced from 26 to 9% by the 2nd year and from 16.8 to 2.8% by the 3rd year. A decrease in the 10-year mortality rate from cardiovascular disorders by 19% among patients undergoing carotid endarterectomy was noted. This operation is recommended in hospitals, where the risk of perioperative complications is less than 6%.

Recommendations

• Carotid endarterectomy is indicated for patients with stenosis of the carotid artery accompanied by symptomatology, more than 70% in centers with perioperative complications (all strokes and death) less than 6% (level of evidence I).
• Carotid endarterectomy can be shown to patients with stenosis of the carotid artery, accompanied by symptomatology, 50-69%. In these cases carotid endarterectomy is most effective in men who underwent hemispheric stroke (level of evidence III).
• Carotid endarterectomy is not recommended for patients with carotid stenosis less than 50% (level of evidence I).
• Before, during and after the operation of carotid endarterectomy, patients should be prescribed antiplatelet therapy (level of evidence: II).
• Patients with contraindications to carotid endarterectomy or with stenosis localized in a surgically inaccessible place can perform carotid angioplasty (level of evidence IV).
• The presence of an atherothrombotic plaque with an uneven (embologenic) surface increases the risk of developing ischemic stroke by 3.1 times.
• Patients with restenosis after carotid endarterectomy can undergo carotid angioplasty or stenting (level of evidence IV).

[23], [24], [25], [26], [27], [28], [29], [30]