Primary prevention

Primary prevention hinges on lifestyle and risk-factor modification. The American Heart Association recommends a blood pressure (BP) target of <130/80 mmHg for adults with an estimated 10-year risk of atherosclerotic cardiovascular disease (CVD) of >10%; and <140/90 mmHg for those at lower risk.[39]​ Lowering BP is associated with a 30% to 40% reduction in stroke risk.[40] Carotid endarterectomy is recommended for significant stenosis.[22] The use of anticoagulation in patients with atrial fibrillation with elevated scores on risk stratification tools such as CHADS2-Vasc or mechanical valves is recommended. Guidelines on antiplatelet use vary based on patients' age and bleeding risk. American College of Cardiology/American Heart Association (ACC/AHA) guidelines state that low-dose aspirin might be considered for primary prevention of atherosclerotic CVD in adults ages 40-70 years who are at higher risk of atherosclerotic CVD but not at increased bleeding risk.[41] The US Preventive Services Task Force (USPSTF) recommends that the decision to initiate low-dose aspirin use for the primary prevention of CVD in adults ages 40-59 years who have a 10% or greater 10-year CVD risk should be an individual one.[42] Evidence indicates that the net benefit of aspirin use in this group is small. Those who are not at increased risk for bleeding and are willing to take low-dose aspirin daily are more likely to benefit.[42] The risk-benefit ratio differs in older patients. The AHA states that low-dose aspirin should not be given routinely for primary prevention of atherosclerotic CVD to adults over 70 years, or to adults of any age who are at increased bleeding risk.[41] The USPSTF recommends against initiating low-dose aspirin use for the primary prevention of CVD in adults ages 60 years or older.[42]

Secondary prevention

In addition to lifestyle and dietary changes, most patients with ischemic stroke or TIA and atherosclerotic disease (intracranial, carotid, aortic, or coronary) should be treated with a statin, with or without ezetimibe, to a goal low-density lipoprotein cholesterol (LDL-cholesterol) of <70 mg/dL (<1.81 mmol/L) to reduce the risk of major cardiovascular events.[21][23] The BMJ: PCSK9 inhibitors and ezetimibe for the reduction of cardiovascular events: a clinical practice guideline with risk-stratified recommendations Opens in new window​

Glucose control (consistent with established guidelines for care of all diabetic patients) is advocated in patients with TIA who have diabetes.

Patients with previously treated hypertension should be restarted on antihypertensive treatment after the first few days of the index event.[39] Patients not previously treated for hypertension who experience a TIA and have an established blood pressure (BP) ≥140/90 mmHg should be prescribed antihypertensive treatment a few days after the index event.[39]

American Heart Association/American Stroke Association (AHA/ASA) guidelines recommend an office BP goal of <130/80 mmHg for most patients to reduce the risk of recurrent stroke and vascular events.[21] The American Academy of Neurology recommends a long-term BP target of <140/90 mmHg in patients with symptomatic intracranial atherosclerotic arterial stenosis.[23]

Drug regimens should be individualized to take into account patient comorbidities, agent pharmacological class, and patient preference.[21][23][39]

Patients with TIA who drink >2 alcoholic drinks a day (men) or >1 alcoholic drink a day (women) should be counseled to eliminate or reduce their consumption of alcohol to reduce stroke risk.[21]

Patients with TIA who smoke are strongly advised to stop smoking. Counseling with or without drug therapy (nicotine replacement, bupropion, or varenicline) is recommended to assist in stopping smoking to reduce risk of recurrent stroke.[21] Avoidance of environmental (passive) tobacco smoke is also recommended.[21]

In patients who are overweight or obese, weight loss is recommended.[21] In patients who are obese, referral to an intensive, multicomponent, behavioral lifestyle-modification program is recommended to achieve sustained weight loss.[21]

Low- to moderate-intensity aerobic activity, muscle-strengthening exercise, and a less sedentary lifestyle is advocated. [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ]

For patients with noncardioembolic ischemic stroke or TIA, guidelines from the AHA/ASA recommend aspirin, clopidogrel, or aspirin/dipyridamole for secondary prevention of ischemic stroke.[21] In patients with high-risk TIA (ABCD2 score ≥4), guidelines from the AHA/ASA recommend that dual antiplatelet therapy should be initiated early (ideally within 12-24 hours of symptom onset and at least within 7 days of onset) and continued for 21 to 90 days, followed by single antiplatelet therapy, to reduce the risk of recurrent ischemic stroke.[21][44] Loading doses are recommended for dual antiplatelet therapy but not for monotherapy.[82][83]​​[84]

The dual antiplatelet therapy regimen of ticagrelor plus aspirin is approved by the Food and Drug Administration (FDA) in the US to reduce the risk for stroke in patients with acute ischemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score of ≤5 or high-risk TIA. The choice of adding ticagrelor or clopidogrel to aspirin should be based on patient factors (e.g., medication adherence, dose frequency).[21] In Europe, an application to the European Medicines Agency (EMA) to change the marketing authorization of ticagrelor to include the prevention of stroke in adults who have had a mild to moderate ischemic stroke or high-risk TIA was withdrawn in December 2021. Based on trial data and the company's response to their questions, the EMA expressed concern that the benefits of short-term treatment with ticagrelor plus aspirin in preventing stroke in these patients did not clearly outweigh the risks of fatal and nonfatal bleeding. The THALES trial of 11,016 patients (none of whom received thrombolysis or thrombectomy or required anticoagulation) demonstrated that compared with aspirin alone, dual treatment with ticagrelor plus aspirin reduced the risk of disabling stroke or death within 30 days (4.0% vs. 4.7%).[83] Severe bleeding was more frequent with ticagrelor plus aspirin than with aspirin alone (0.5% vs. 0.1%), including in those with intracranial hemorrhage (0.4% vs. 0.1%). For people with recent stroke with NIHSS score of <5, ticagrelor plus aspirin for 30 days was more effective in preventing recurrent ischemic stroke than aspirin alone.[83]

Anticoagulation therapy is superior to antiplatelet therapy for prevention of cardioembolic strokes and should be started within the first 2 weeks. In patients with nonvalvular atrial fibrillation and stroke or TIA, oral anticoagulation (e.g., apixaban, dabigatran, edoxaban, rivaroxaban, or warfarin) is recommended to reduce the risk of recurrent stroke, regardless of whether the atrial fibrillation pattern is paroxysmal, persistent, or permanent.[21] Direct-acting oral anticoagulants (DOACs), such as apixaban, dabigatran, edoxaban, or rivaroxaban, are recommended over a vitamin K antagonist, e.g., warfarin, in patients with stroke or TIA and atrial fibrillation who do not have moderate to severe mitral stenosis or a mechanical heart valve.[21] Large randomized trials have shown DOACs to clinically reduce the risk of thrombotic stroke with less bleeding risk compared with vitamin K antagonists.[21][97][98] DOACs have the significant advantage of fast onset, predictable dosing requirements, and eliminating the need for monitoring.[99] Disadvantages include higher drug cost and inability to reliably monitor anticoagulant effect using prothrombin time (PT), international normalized ratio (INR), or partial thromboplastin time (PTT). Patients with valvular atrial fibrillation (i.e., moderate to severe mitral stenosis or mechanical heart valves) should be treated with warfarin. Range INR for patients on warfarin should be 2.0 to 3.0.[21] Mitral mechanical prosthetic valves require a higher INR goal of 3.0.[21] Antiplatelet therapy continues to be recommended over warfarin in patients with ischemic stroke or TIA and native aortic or nonrheumatic mitral valve disease (e.g., mitral annular calcification or mitral valve prolapse) who do not have atrial fibrillation or another indication for anticoagulation.[21] Dabigatran is contraindicated in people with mechanical heart valves. Apixaban, edoxaban, and rivaroxaban have not been studied in patients with prosthetic heart valves and are not recommended in these patients.

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