How do you prevent ischemic stroke?

Screening

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

Considering the close connection between obstructive lesions of the brachiocephalic arteries and the development of ischemic stroke and the widespread development of surgical methods for the prevention of cerebrovascular accidents, a promising direction is the use of ultrasound diagnostic methods for screening for lesions of the brachiocephalic arteries with subsequent implementation of a set of preventive measures, including surgical methods. Usually, screening for obstructive lesions of the brachiocephalic arteries is performed for people over 40 years of age 1-2 times a year. Screening for heart disease, in particular atrial fibrillation, is also recognized as an important task in the prevention of ischemic stroke.

Primary prevention of ischemic stroke

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

The mass strategy is to achieve positive changes in each person in the general population by influencing modifiable risk factors. The high-risk strategy involves early identification of patients from high-risk groups for stroke (e.g., with arterial hypertension or hemodynamically significant stenosis of the internal carotid artery) with subsequent preventive drug and (if necessary) vascular surgical treatment, which can reduce the incidence of stroke by 50%. Stroke prevention should be individualized and include non-drug measures, targeted drug or vascular surgical treatment.

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

The mass (population) strategy is aimed at informing the population about modifiable 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 media and issuing special leaflets and posters, as well as medical examination of the population in accordance with the primary prevention algorithm. According to this algorithm, based on the results of examination and consultation with narrow specialists, patients are assigned to various dispensary groups:

• Group A - practically healthy (repeat examination after 2-3 years);
• Group B - individuals with risk factors for cardiovascular diseases, but without clinical manifestations of neurological disorders, as well as patients in whom carotid noise was detected during auscultation of the neck vessels;
• Group B - patients with risk factors for cardiovascular diseases and clinical manifestations of neurological disorders.

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

Patients in 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 foods and following a diet, increasing physical activity, maintaining a body mass index of less than 25 kg/m2 ^or reducing body weight by 5-10% of the initial weight.

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

In diabetes, it is important to maintain optimal blood glucose levels.

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

In cases of carotid artery stenosis of more than 60%, including asymptomatic, the possibility of endarterectomy is considered, taking into account the age of the patient and the risk of developing postoperative complications. In recent years, vascular angioplasty (stenting) has been used.

It is important to note the importance of quitting smoking or significantly reducing the number of cigarettes smoked, as 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 risk level of non-smokers.

The protective effect of physical exercise is partly related to the reduction in body weight and blood pressure, as well as to its role in reducing fibrinogen levels and increasing the fibrinolytic activity of tissue plasminogen activator in blood plasma, high-density lipoprotein concentrations and glucose tolerance.

All patients should be advised to reduce their intake of table salt, increase their intake of fruits and vegetables, and eat fish at least twice a week. People who eat fatty sea fish and salmon 2-4 times a week have a 48% lower risk of stroke than those who eat fish only once a week.

In the last 5 years, several programs aimed at primary prevention of vascular diseases have been implemented: programs to combat arterial hypertension, a nationwide program for the integrated prevention of non-communicable diseases (CINDI), a program for the medical examination of the working-age population with the identification of risk groups and prevention. The introduction of primary prevention allows us to prevent at least 150 cases of stroke per 100,000 people in 3-5 years.

Secondary prevention of ischemic stroke

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

Individualized secondary stroke prevention has been shown to reduce the risk of recurrent cerebrovascular accidents by 28-30%. Overall, the economic costs of stroke prevention are significantly lower than the costs required for treatment and medical and social rehabilitation of patients who have suffered a stroke, as well as their disability pension. The data presented show how important it is to develop an adequate system to prevent recurrent cerebrovascular accidents.

Data from numerous international studies and systematic reviews demonstrate, as a rule, the effectiveness of one of the directions of secondary stroke prevention, while the greatest result can be achieved by using a complex of preventive measures. A comprehensive program of secondary stroke prevention is based on the principles of evidence-based medicine and a polytherapeutic approach. It includes 4 directions: hypotensive (diuretics, angiotensin-converting enzyme inhibitors), antithrombotic (antiplatelet agents, indirect anticoagulants), lipid-lowering therapy (statins), as well as surgical treatment for carotid artery stenosis (carotid endatherectomy).

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

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

The goal of secondary prevention of cerebral stroke, based on an individual approach to therapeutic measures, is to reduce the risk of recurrent cerebral stroke and other vascular pathologies (for example, myocardial infarction, peripheral vascular thrombosis, pulmonary embolism, etc.), and increase the life expectancy of patients. Direct adequate criteria for assessing the effectiveness of therapeutic measures are considered to be a decrease in the incidence of recurrent stroke and an increase in life expectancy.

The criteria determining the choice of secondary prevention strategy for cerebral stroke are as follows:

• risk factors for stroke;
• pathogenetic type of stroke, both current and previously suffered;
• results of instrumental and laboratory examination, including an assessment of the condition of the main arteries of the head and intracerebral vessels, the cardiovascular system, rheological properties of the 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 be started in a hospital setting from the 2nd-3rd day of the disease. If secondary prevention was not recommended in the hospital or the patient was treated at home, therapy is selected by a neurologist in a polyclinic based on an additional examination (if not previously performed), including ECG, Holter monitoring if necessary (to exclude transient rhythm disturbances and detect atrial fibrillation), as well as ultrasound methods (to determine the degree of stenosis of the main arteries of the head) and a study of the lipid spectrum of the blood (to determine hyperlipidemia). After therapy is selected, the patient is monitored in a polyclinic setting by a general practitioner once every 3 months during the first year, and then every six months. During visits, the patient's condition is assessed and everything that has happened since the last visit is analyzed (vascular disorders, hospitalizations, side effects).

Antihypertensive therapy

High blood pressure is the most important risk factor for cerebral stroke. A meta-analysis of the results of 4 randomized clinical trials that studied the efficacy of diuretics and the beta-blocker atenolol in arterial hypertension in patients who had suffered a stroke, regardless of the blood pressure level, revealed an insignificant decrease in the frequency of repeated cerebrovascular accidents by 19%, i.e. only a tendency towards a rarer development of repeated stroke against the background of a decrease in blood pressure was noted.

It has been proven that today the most effective of all antihypertensive drugs in preventing recurrent cerebrovascular accidents are the angiotensin-converting enzyme inhibitor perindopril and the angiotensin II receptor blocker eprosartan.

When speaking about antihypertensive therapy as secondary prevention of stroke, it should be remembered that we are talking not only about lowering blood pressure to a target level in patients with arterial hypertension, but also about therapy that prevents further remodeling and hypertrophy of the vascular wall, progression of atherosclerotic damage, including in patients with normal blood pressure.

Recommendations

• The drugs of choice for secondary prevention of recurrent cerebrovascular accident 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 incidence of recurrent cerebrovascular accidents not only in hypertensive patients, but also in normotensive patients due to the additional angioprotective, antiatherogenic and organoprotective properties of these drugs (level of evidence I).
• Although there is no convincing evidence, blood pressure should not be excessively reduced in patients at risk of developing hemodynamic stroke due to occlusive or severe stenotic lesions of the carotid or vertebrobasilar arteries (level of evidence II).
• Non-drug interventions for hypertension should include stopping smoking, limiting salt intake, reducing excess body weight, optimizing physical activity levels, limiting alcohol consumption, and reducing the effects of chronic stress, which in itself can lead to increased blood pressure (evidence level II).

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Antithrombotic therapy

Antithrombotic therapy includes the administration of antiplatelet and anticoagulant drugs.

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Antiplatelet therapy

An important role in the pathogenesis of acute cerebrovascular accidents is attributed to atherothrombosis and changes in the rheological properties of the blood, including an increase in the aggregation capacity of platelets and erythrocytes. Increased platelet aggregation activity and massive formation of thromboxane A ₂, detected in atherothrombosis of the main vessels of the head, can be considered adequate markers of hemostatic activation, characteristic of both thrombus formation and atherogenesis. In the residual period of stroke, the reduction of the athrombogenic reserve of the vascular endothelium increases (i.e., acute cerebrovascular accident), exerting a significant effect on the hemostatic potential of the blood and the vascular system of the brain, which can aggravate the process of depletion of the athrombogenic potential of the vascular system, thereby contributing to the progression of atherothrombosis.

A systematic review of antiplatelet studies provided clear evidence of benefit from antiplatelet therapy: long-term antiplatelet therapy reduces the risk of major vascular events (eg, myocardial infarction, stroke, vascular death) by 25%. Studies evaluating antiplatelet therapy in patients with a history of stroke or transient ischemic attack showed that this therapy reduces the 3-year risk of major vascular events from 22% to 18%, equivalent to preventing 40 major vascular events per 1000 patients treated (i.e., 25 high-risk people would need to be treated with antiplatelet drugs for 3 years to avoid one vascular event).

The advantages of antithrombotic therapy have been proven in various multicenter studies. A meta-analysis of randomized trials examining the effectiveness of various antiplatelet agents and their combinations in preventing recurrent cerebrovascular accidents showed that they have approximately the same preventive effect. The range of drugs with antiplatelet action is quite wide, which allows each patient to select the optimal treatment, taking into account the individual characteristics of central and cerebral hemodynamics, vascular reactivity, and the condition of the vascular wall. When selecting patients, it is necessary to take into account the risk factors for the development of recurrent stroke in a particular patient (the presence of arterial hypertension, diabetes mellitus, heart disease, etc.) and the results of examination using additional methods. Since the effects of the antithrombotic agents used do not differ significantly, the choice of drug should be based on its safety, the absence of side effects, and the characteristics of hemostasis in a particular patient.

To date, the most studied effectiveness of acetylsalicylic acid, dipyridamole and clopidogrel in the prevention of recurrent cerebrovascular accidents has been the effectiveness of acetylsalicylic acid, dipyridamole and clopidogrel.

• Acetylsalicylic acid is the most widely used antiplatelet drug. The main mechanism of action of acetylsalicylic acid is the inactivation of the cyclooxygenase enzyme, which results in disruption of the synthesis of prostaglandins, prostacyclins and irreversible disruption of the formation of thromboxane A ₂ in platelets. The drug is prescribed in a dose of 75-100 mg / day (1 mcg / kg), released with a special enteric coating or as a combination drug with an antacid component.
• Dipyridamole, a pyrimidine derivative with primarily antiplatelet and vascular effects, is the second drug used for secondary stroke prevention. Dipyridamole is a competitive inhibitor of adenosine deaminase and adenyl phosphodiesterase, which increases the levels of adenosine and cAMP in platelets and vascular smooth muscle cells, preventing the inactivation of these substances. Dipyridamole is prescribed at a dose of 75-225 mg/day.
• Clopidogrel (Plavice) is a selective, non-competitive antagonist of platelet receptors to 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 recurrent cerebrovascular accident, adequate antiplatelet therapy should be administered (level of evidence I).
• Acetylsalicylic acid at a dose of 100 mg effectively reduces the risk of recurrent 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).
• Dipyridamole at a dose of 75-225 mg/day along with acetylsalicylic acid is effective in secondary prevention of ischemic disorders (level of evidence I). It can be the drug of choice in patients with intolerance to acetylsalicylic acid (level of evidence II).
• The combination of acetylsalicylic acid (50 mg) and sustained-release dipyridamole (150 mg) is more effective than acetylsalicylic acid alone in preventing recurrent cerebrovascular accidents (level of evidence I). This combination can be recommended as the treatment of choice (level of evidence I).
• Clopidogrel (Plavice) 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 to patients with intolerance to acetylsalicylic acid and dipyridamole (level of evidence IV), as well as to high-risk patients (with ischemic heart disease and/or atherothrombotic lesion of peripheral arteries, diabetes mellitus) (level of evidence II).
• The combination of aspirin (50 mg) and clopidogrel (75 mg) is more effective than monotherapy with these drugs in preventing recurrent stroke. However, the risk of life-threatening bleeding is twice that of monotherapy with clopidogrel or aspirin (level of evidence I).
• In patients without cardiac sources of embolism who have had a recurrent stroke while receiving acetylsalicylic acid, taking anticoagulants (warfarin) does not bring any benefit (level of evidence I).

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Anticoagulant therapy

Thromboembolism from the heart cavities is the cause of every sixth ischemic stroke. Atrial fibrillation is the main cause of thromboembolic strokes, the risk of recurrent cerebrovascular accident is 12% per year. Antithrombotic drugs are used for long-term secondary prevention after transient ischemic attack and ischemic stroke in patients with atrial fibrillation. The drug of choice is the indirect anticoagulant warfarin, which has proven its effectiveness in the primary prevention of vascular disorders in patients with a high risk of thromboembolic complications. Several major randomized clinical trials have been conducted to determine the tactics of antithrombotic therapy in patients with atrial fibrillation who have suffered an ischemic stroke and to prove the superiority of anticoagulants over acetylsalicylic acid.

Recommendations

• Warfarin is effective in preventing recurrent cerebrovascular accidents in patients with non-valvular atrial fibrillation (level of evidence I).
• Target values of the international normalized ratio that ensure reliable prevention of ischemic manifestations correspond to 2.0-3.0 (level of evidence I). High rates of mortality and serious bleeding have been noted in patients with excessive hypocoagulation (international normalized ratio >3.0) (level of evidence I).
• There is currently no convincing evidence on the effectiveness of warfarin in the prevention of non-cardiogenic ischemic strokes (level of evidence I).

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Hypolipidemic therapy

High plasma cholesterol is a significant risk factor for atherosclerosis and its ischemic complications. Hypolipidemic agents have proven themselves in cardiology practice as drugs for primary and secondary prevention of myocardial infarction. However, the role of statins in preventing strokes is not so clear. Unlike acute coronary episodes, where the main cause of myocardial infarction is coronary atherosclerosis, atherosclerosis of a large artery causes stroke in less than half of cases. In addition, no clear correlation has been found between the incidence of strokes and blood cholesterol levels.

Nevertheless, a number of randomized clinical trials on primary and secondary prevention of coronary heart disease have shown that therapy with lipid-lowering drugs, namely statins, reduces the incidence of not only coronary disorders, but also cerebral stroke. An analysis of 4 major studies that examined the effectiveness of lipid-lowering therapy for secondary prevention of coronary heart disease showed that statin therapy reduces the total incidence of strokes. Thus, in the 4S study, 70 strokes occurred in the group of patients who received simvastatin at a dose of 40 mg for an average of 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 at a dose of 40 mg/day demonstrated its effectiveness in the randomized clinical trial PROSPER (The PROspective Study of Pravastatin in the Elderly at Risk). The drug significantly reduced the risk of coronary mortality and the incidence of myocardial infarction, and the risk of recurrent cerebrovascular accidents decreased by 31%, although the incidence of fatal strokes did not change. Pravastatin effectively prevented cerebrovascular accidents in patients over 60 years of age without arterial hypertension and diabetes mellitus, with an ejection fraction of more than 40%, and in patients with a history of acute cerebrovascular accident.

It should be noted that all data supporting the need to use statins to prevent cerebral strokes are obtained from studies whose main goal was to identify a reduction in the frequency of coronary episodes. In this case, as a rule, they analyzed how statin therapy affects the reduction in the total frequency of stroke without taking into account anamnestic data on whether the stroke was primary or recurrent.

Recommendations

• Patients who have suffered a transient ischemic attack or ischemic stroke in the presence of ischemic heart disease, atherothrombotic peripheral arterial disease, or diabetes mellitus should receive treatment that includes lifestyle changes, dietary nutrition, and drug therapy (evidence level II).
• It is recommended to maintain the target level of low-density lipoprotein cholesterol in patients with coronary heart disease or atherothrombotic disease of the arteries of the lower extremities 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 stroke (evidence level II).
• Currently, there is no convincing evidence on the need to use statins in the acute period of cerebral stroke (level of evidence I).
• The use of statins in patients who have had a hemorrhagic stroke requires special caution. The decision on such treatment is made taking into account all risk factors and comorbidities (level of evidence II).

Carotid endarterectomy

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

Recommendations

• Carotid endarterectomy is indicated for patients with symptomatic carotid artery stenosis greater than 70% in centers with perioperative complication rates (all strokes and death) less than 6% (evidence level I).
• Carotid endarterectomy may be indicated in patients with symptomatic carotid artery stenosis of 50-69%. In these cases, carotid endarterectomy is most effective in men who have had a hemispheric stroke (evidence level III).
• Carotid endarterectomy is not recommended in patients with carotid artery stenosis less than 50% (level of evidence I).
• Before, during, and after carotid endarterectomy surgery, patients should be given antiplatelet therapy (level of evidence II).
• In patients with contraindications to carotid endarterectomy or with stenosis localized in a surgically inaccessible location, carotid angioplasty can be performed (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 may undergo carotid angioplasty or stenting (evidence level IV).

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