The new American Heart Association (AHA)/American Stroke Association (ASA) guidelines for secondary prevention of stroke and transient ischemic attack (TIA) were developed by Dr. Furie, director of the Massachusetts General Hospital Stroke Service, and a writing committee of 18 experts to provide clinicians with the latest evidence-based recommendations for preventing ischemic stroke and stroke recurrence in TIA survivors. The aim is to provide clinicians with the latest evidence-based recommendations for preventing ischemic stroke and stroke recurrence in TIA survivors.
The guidelines cover all aspects of secondary prevention of stroke and TIA, including the definition and staging of TIA, control of risk factors, interventional treatment of atherosclerotic disease, antithrombotic therapy for cardiac stroke, antiplatelet agents for non-cardiac stroke, prevention of stroke recurrence in special circumstances, and specific implementation methods and application of the guidelines in high-risk groups. The biggest improvement over the previous guidelines is the promotion of individualized treatment, with all recommendations emphasizing the selection of appropriate preventive treatment for individual patients.
1. Definition of TIA and staging of ischemic stroke
The new guidelines define TIA as transient neurological deficits caused by focal ischemia of the cerebrospinal cord or retina without acute infarction. The duration of symptoms of TIA is not mentioned.
The new guidelines still use the traditional TOAST typing, which classifies ischemic stroke into 5 types according to clinical manifestations, imaging data, and relevant vascular examinations: atherosclerotic, cardiogenic, small artery occlusive, and other causes and etiology unknown.
2. Control of risk factors
2. 1 Hypertension antihypertensive treatment needs to follow the principle of individualization, and it is recommended to select the appropriate treatment regimen according to drug properties, mechanism of action, and patient characteristics ( Class IIa; Level B evidence), which is a new opinion of the guideline. The new guideline, based on a pooled analysis of the Heart Turnover Prevention Evaluation Study (HOPE), the Perindopril Recurrent Stroke Prevention Study (PROGRESS), and the Association of Antihypertensive and Secondary Stroke Prevention Study, recommends that antihypertensive treatment reduces the recurrence rate of all types of stroke regardless of previous hypertension (Class IIa; Level B evidence) and recommends antihypertensive treatment 24 h after onset of stroke (Class I; Level A evidence). Evidence).
An average reduction in blood pressure of 10/5 mmHg reduces the risk of stroke (Class IIa; Level B). The new guidelines recommend applying the criteria and recommendations of the Joint Committee on Prevention, Detection, Evaluation, and Treatment of Hypertension, 7th Report (JNC-7), which set a normal blood pressure value of <120/80 mmHg (Class IIa; Level B evidence) and emphasize the importance of lifestyle changes for blood pressure control, recommending reduced body mass, increased activity, limited alcohol consumption, and a proper diet (Class IIa; Level C evidence).
In addition, the new guidelines summarize the results of the Dutch TIA trial, the Post Stroke Antihypertensive Treatment Trial (PATS), and the HOPE and PROGRESS trials, which concluded that diuretics or diuretics in combination with angiotensin-converting enzyme inhibitors may prevent stroke recurrence (Class I; Level A evidence).
2. 2. 2 Diabetes mellitus Diabetes mellitus is an independent risk factor for stroke. The new guidelines continue to follow the current guidelines for glycemic and blood pressure management, recommending glycosylated hemoglobin levels ≤7% and target blood pressure <130/80 mmHg (Class I; Level B evidence).
2. 3 The results of the Study on the Prevention of Stroke with Intensive Lipid Lowering (SPARCL) showed that statins have a dual preventive effect on stroke and coronary artery disease. Therefore, the new guidelines recommend that patients with atherosclerotic stroke without a history of coronary artery disease or LDL-C ≥100 mg/dl (2. 6 mmol/L) be given statins as appropriate (Class I; Level B evidence), with the greatest benefit of reducing LDL-C by 50% or achieving a target LDL-C <70 mg/dl (1. 8 mmol/L) (Class IIa; Level B evidence).
Patients with ischemic stroke or TIA with a history of coronary artery disease who have high cholesterol are recommended to be addressed by the National Cholesterol Education Program’s Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Cholesterol in Adults: Lifestyle Changes, Dietary Changes, and Medications (Class I; Level A Evidence).
In addition, the Veterans High Density Protein Intervention Trial demonstrated that treatment with niacin or gemfibezil in patients with HDL-C < 40 mg/dl reduced the recurrence of cerebrovascular events, so the new guidelines state that patients with low HDL-C may be treated with niacin or gemfibezil (Class IIb; Level B Evidence).
2.4 Smoking or passive smoking can increase the risk of cardiovascular disease. New guidelines recommend that patients with a history of stroke or TIA who smoke quit (Class I; Level C evidence), including through persuasion, nicotine product replacement, and oral smoking cessation medication (Class I; Level A evidence). Passive smoking (Class IIa; Level C) should be avoided as much as possible.
2. 5 Studies have found that heavy alcohol consumption increases the risk of stroke and can lead to alcohol-induced hypertension, hypercoagulability of the blood, post-infarction atrial fibrillation, insulin resistance and metabolic syndrome. The new guidelines take into account the advice of the US Preventive Services Task Force, which recommends eliminating or reducing alcohol consumption in heavy drinkers (Class I; Level C evidence) and that light to moderate drinking (no more than 1 drink in men) may not be dangerous but is not recommended for non-drinkers (Class IIb; Level B evidence).
2. 6 Physical activity studies have found that maintaining moderate exercise reduces the incidence of stroke by 20% and high activity levels reduce the incidence of stroke by 27%. The new guidelines promote exercise (Class IIb; Level C evidence).
The new guidelines include metabolic syndrome as a risk factor to be controlled for secondary prevention of stroke for the first time, and 40% to 50% of patients with cerebral infarction have metabolic syndrome. The Warfarin and Aspirin in Intracranial Disease Trial (WASID) confirmed that the metabolic syndrome increases the risk of death from diabetes, cardiovascular disease, and other causes.
Lifestyle improvements to reduce body mass can improve insulin sensitivity and improve various abnormalities in the metabolic syndrome (Class I; Level C evidence). There are no studies on primary and secondary prevention of stroke in patients with metabolic syndrome, and until these studies are completed, the criteria for secondary prevention in patients with metabolic syndrome need to refer to the appropriate guidelines for patients without metabolic syndrome (Class I; Level A evidence).
3. Recommendations for interventional treatment of patients with large atherosclerotic strokes
According to the European Carotid Surgery Trial (ECST), the North American Symptomatic Carotid Endarterectomy Trial (NASCET), and the Veterans Administration Cooperative Study (VACS), CEA plus drug therapy is superior to drug therapy alone in symptomatic patients with >70% non-invasive imaging of internal carotid artery stenosis (Class I; Level A evidence). Evidence).
The choice of treatment for symptomatic patients with 50% to 69% stenosis is debated. The optimal duration of CEA is debated, with the accepted duration being 2 to 6 weeks, and the most recent findings suggesting the greatest benefit for CEA in men >75 years of age within 2 weeks of onset (Class IIa; Level B evidence). Compared to CEA, CAS is less invasive, less painful, and has a faster recovery, but its durability has not been proven.
CAS is primarily used in patients at high risk for open endarterectomy (Class I; Level B evidence). There are no studies demonstrating that EC/IC bypass surgery can benefit patients with carotid occlusion or distal branch stenosis. Therefore, the new guidelines do not recommend EC/IC bypass surgery (Class III; Level A evidence). The new guidelines consider optimal pharmacologic therapy to be appropriate for all patients with carotid stenosis and recommend a combination of surgical and pharmacologic options (Class I; Level B evidence).
3. 2 A systematic review of extracranial vertebrobasilar artery lesions showed that patients with symptomatic vertebral artery stenosis had a higher risk of recurrent stroke at 7 d after the onset of symptoms than patients with symptomatic carotid stenosis. Because of the high morbidity and mortality associated with surgical treatment, pharmacologic therapy has been the primary treatment modality for this disease (Class I; Level B evidence). Revascularization may be considered when pharmacologic therapy is not effective (Class IIb; Level C evidence).
3. 3 The WASID trial of intracranial atherosclerosis found an increased risk of bleeding with warfarin for symptomatic intracranial atherosclerosis, so the guidelines recommend aspirin (Class I; Level B evidence). Based on safety and efficacy, the recommended dose of aspirin in the new guideline is 50 to 325 mg/d (Class I; Level B evidence). The new guideline suggests that long-term maintenance of BP < 140/90 mmHg and total cholesterol levels < 200 mg/d may reduce the recurrence rate of stroke based on the results of the WASID trial data analysis (Class IIb; Level B evidence).
For intracranial revascularization and stenting, trials are still ongoing, and the new guidelines do not provide clear recommendations for the use of these procedures (Class IIb; Level C evidence). Analysis of studies on bypass surgery has confirmed that its efficacy is much worse than that of drug therapy, and the new guideline discards these procedures (Class III; Level B evidence).
The new guidelines do not change the recommendations for the treatment of cardiogenic cerebral embolism, except that recent studies have shown that the combination of aspirin and clopidogrel increases the risk of bleeding, and therefore the new guidelines do not recommend the combination of aspirin and clopidogrel in patients with contraindications to warfarin. Numerous trials have demonstrated the overwhelming benefit of warfarin in preventing cardiogenic stroke.
The optimal dosage of oral anticoagulants for stroke prevention in patients with atrial fibrillation is to maintain an INR of 2 to 3 (Class I; Level A evidence), and the effect of anticoagulants decreases significantly with an INR < 2, with a corresponding increase in the risk of bleeding. Therefore, the new guidelines do not recommend the combination of both drugs (Class III; Level B evidence).
Patients with cardiogenic stroke are at increased risk of stroke recurrence when oral anticoagulation is suspended, and the new guideline recommends bridging therapy with subcutaneous low-molecular-weight heparin (Class IIa; Level C evidence). Anticoagulation should also be used in acute myocardial infarction and postinfarction appendage thrombosis, dilated cardiomyopathy, rheumatic mitral valve disease, and prosthetic valve use, with an INR target of 2.5 (Class I; Level B evidence). Aspirin is recommended for patients with mitral valve prolapse, calcification, or aortic valve disease who cannot be treated with anticoagulation (Class IIb; Level C evidence).
3. 5 For antithrombotic therapy of noncardiogenic embolic stroke or TIA, the old guidelines recommended aspirin and clopidogrel in parallel, and the new guidelines recommend aspirin in Class I/A only. The new guideline does not recommend aspirin in combination with clopidogrel (Class III; Level A evidence).
The results of the ESPRIT study showed that the combination of aspirin and disopyramide reduced the incidence of the primary endpoint by 20% and the absolute risk by 1% per year. The results of this study raised the recommendation for aspirin in combination with extended-release disopyramide from Class II/A to Class I/B.
4. Other special cases of stroke
4. 1 Fabry disease is mentioned for the first time in the new guideline. For patients with ischaemic stroke or TIA due to this disease, the guideline states that all measures of secondary stroke prevention are appropriate and recommends the administration of alpha-galactosidase replacement therapy (Class I; Level B evidence).
4. 2 Patients with ischaemic stroke or TIA in pregnancy who are at high risk of stroke thromboembolism may be treated with subcutaneous normal or low molecular heparin injections during pregnancy, but APTT and anti-Xa factors should be monitored and heparin dosage adjusted as appropriate. Treatment with normal/low-molecular heparin may be given until week 13, followed by warfarin until the end of the third trimester, and then back on normal/low-molecular heparin until delivery. In the absence of a high risk of thromboembolism, regular heparin/low-molecular heparin may be considered for the first trimester of pregnancy, followed by low-dose aspirin (Heparin) for the rest of pregnancy.
In addition, the new guidelines still do not recommend postmenopausal hormone replacement therapy for female patients (Class III; Level A evidence).
4. 3 Use of anticoagulants after intracranial hemorrhage The new guidelines provide clearer recommendations on the use of anticoagulants after intracranial hemorrhage. Antiplatelet agents may be considered in patients with a relatively low risk of cerebral infarction and a high risk of amyloid angiopathy or in patients with very poor overall neurologic function.
For patients with a high risk of thromboembolism, reintroduction of warfarin should be considered, and it is reasonable to restart warfarin therapy within 7 to 10 d after the onset of cerebral hemorrhage (Class IIb; Level B evidence). For heparin-related post-stroke cerebral hemorrhage, the new guideline recommends the use of arginine sulfate at a dose that depends on the time of heparin cessation (Class I; Level B evidence).
The new guidelines also pay special attention to real-life practice issues and recommend specific implementation strategies. The new guidelines recommend the development of standardized measures to improve stroke prevention and treatment in the elderly, socioeconomically disadvantaged and high-risk ethnic groups who are not only at high risk of stroke but also poor adherents to the guidelines. The new guidelines recommend the development of standardized prevention and treatment measures and greater efforts to improve stroke prevention and treatment.