Primary prevention
Established measures for primary prevention of stroke include physical activity; healthy sleep; avoidance of obesity; appropriate diet; treatment of hypertension, hypercholesterolemia, and diabetes; and abstinence from smoking, illegal drug use, and heavy drinking.[41][85][109][110] The American Heart Association (AHA) ‘Essential 8’ serve as an educational tool for the prevention of all forms of cardiovascular disease in the general population. The 8 strategies are as follows: ‘eat better, be more active, quit tobacco, get healthy sleep, manage weight, control cholesterol, manage blood sugar, and manage blood pressure'. American Heart Association: Life's Essential 8 Opens in new window
Further preventive measures may be appropriate in particular patient groups.
Prevention of further stroke in a patient with transient ischemic attack (TIA) is classed as secondary prevention.
Anticoagulation and atrial appendage closure for people with atrial fibrillation
Compared with antiplatelet therapy, adjusted-dose warfarin and related oral anticoagulants reduce the risk of stroke, disabling stroke, and other major vascular events by about one third in people with nonvalvular atrial fibrillation.[111] The benefits of anticoagulation therapy should be weighed against the risk of hemorrhage, particularly intracranial hemorrhage, for each patient.
In patients with nonvalvular atrial fibrillation, direct oral anticoagulants (DOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban are as effective as warfarin in preventing stroke, carry a smaller risk of intracranial bleeding, and there is no need to check coagulation laboratory studies. Warfarin remains the choice for thromboembolic prevention in patients with mechanical heart valves.[112][113]
In patients with atrial fibrillation, surgical left atrial appendage closure may be beneficial in reducing the risk of stroke. Of patients with nonvalvular atrial fibrillation who have a stroke, the left atrial appendage is the location of identified thrombus 90% of the time.[113] In a randomized trial of 2379 patients with atrial fibrillation, ischemic stroke or systemic embolism at 3.8 years occurred in 4.8% of the occlusion of the left atrial appendage group compared with 7.0% of the no occlusion group.[114] Most of these patients (75%) continued to receive ongoing antithrombotic therapy. The Food and Drug Administration (FDA) has approved two devices for atrial appendage closure. However, the efficacy of left atrial appendage closure compared with DOACs is unknown.[113] In patients at high bleeding risk from oral anticoagulation, left atrial appendage closure can reduce the long-term risk of bleeding with an ischemic stroke risk comparable to that of anticoagulation with a vitamin K antagonist (usually warfarin).[113]
Treatment of hyperlipidemia
In adults who qualify for treatment with lipid-lowering therapy according to guidelines, treatment with a statin is recommended to reduce the risk of a first stroke.[41]
Use of the cholesterol-lowering agent ezetimibe is associated with reduced stroke risk.[115][116]
There is a strong evidence base for the benefits of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor monoclonal antibodies (e.g., evolocumab, alirocumab), and that they reduce low-density lipoprotein (LDL)-cholesterol (LDL-C).[41][117] BMJ: PCSK9 inhibitors and ezetimibe for the reduction of cardiovascular events Opens in new window Evolocumab reduced lipids and cardiovascular events in patients with hyperlipidemia compared with standard therapy.[118][119] Evolocumab has been approved by the FDA and the European Medicines Agency (EMA) for the reduction of LDL-C in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin, or alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant or for whom a statin is contraindicated. Alirocumab significantly reduced LDL levels in patients with heterozygous familial hypercholesterolemia receiving statin therapy at the maximum tolerated dose.[120] In one multicenter, randomized, double-blind, placebo-controlled trial of patients who had a previous acute coronary syndrome and who were receiving high-intensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower among those who received alirocumab than among those who received placebo.[121]
Inclisiran is an alternative PCSK9 inhibitor. It is a small interfering RNA drug, not a monoclonal antibody like the other available PCSK9 inhibitors. Inclisiran is approved for primary hyperlipidemia (including heterozygous familial hypercholesterolemia [HeFH]) as an adjunct therapy for patients on maximally tolerated statin therapy.[122][123]
Antiplatelet therapy
Patients without preexisting atherosclerotic cardiovascular disease (CVD): guidelines vary based on patients’ age and bleeding risk. 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.[124] 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 aged 40-59 years who have a 10% or greater 10-year CVD risk should be an individual one.[125] 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.[125] The risk-benefit ratio differs in older patients. AHA guidelines state 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.[124][126][127][128] The USPSTF recommends against initiating low-dose aspirin use for the primary prevention of CVD in adults 60 years or older.[125]
Patients with preexisting coronary artery disease or peripheral artery disease: In one large randomized controlled trial, patients with preexisting coronary artery disease or peripheral artery disease were given aspirin alone, rivaroxaban alone, or low-dose rivaroxaban plus aspirin. During a mean follow-up of 23 months, fewer patients had strokes in the low-dose rivaroxaban plus aspirin group than in the aspirin group (83 [0.9% per year] vs. 142 [1.6% per year]). Ischemic/uncertain strokes were reduced by nearly half (68 [0.7% per year] vs. 132 [1.4% per year]), and fatal and disabling strokes were also decreased by the combination (32 [0.3% per year] vs. 55 [0.6% per year]). Therefore, low-dose rivaroxaban plus aspirin appears to offer significant primary and secondary stroke prevention in this population.[129]
The table that follows summarizes recommendations on the primary prevention of ischemic stroke and transient ischemic attack (TIA) taken from the American Heart Association/American Stroke Association (AHA/ASA) guideline for the primary prevention of stroke.[41]
Recommendations on screening are described in the guideline, but note that they are not outlined in the table. Use a risk prediction instrument that estimates risk for atherosclerotic CVD broadly rather than cerebrovascular disease alone, such as the Pooled Cohort Equations (ASCVD Risk Estimator). ACC/AHA: ASCVD Risk Estimator Opens in new window
Note that an individual patient may fall into more than one group and so interventions might be additive; please review all population and subpopulation groups to assess all that apply.
Adult with hypertension
Stage 1 hypertension: systolic blood pressure (SBP) of 130 to 139 mmHg or diastolic blood pressure (DBP) of 80 to 89 mmHg. Stage 2 hypertension: SBP ≥140 mmHg or DBP ≥90 mmHg.
All
Intervention
Optimal management of hypertension
Optimize hypertensive control with nonpharmacologic interventions (lifestyle improvements) with or without pharmacologic treatment; treatment is individualized based on the stage of hypertension as well as according to cardiovascular risk.
Pharmacologic treatment with antihypertensive medication is recommended:
in all adults with stage 2 hypertension; or
in those with stage 1 hypertension at higher risk for atherosclerotic CVD.
The following drugs are recommended as initial antihypertensive drug therapies to prevent stroke:
Thiazide and thiazide-like diuretics
Calcium-channel blockers
ACE inhibitors
Angiotensin-II receptor antagonists
Goal
Reduced risk of ischemic stroke and TIA
For those requiring pharmacologic treatment, a treatment target of <130/80 mmHg is recommended to prevent stroke.
In most adults with hypertension, a treatment regimen incorporating ≥2 antihypertensive medications is indicated to achieve the blood pressure (BP) control necessary to prevent stroke.
Ages ≥60 years; with uncontrolled BP (SBP ≥140mmHg if taking antihypertensive medication or ≥160 mmHg if not)
Intervention
Consider use of a salt substitute
Salt substitution (with 75% sodium chloride and 25% potassium chloride) compared with the use of regular salt (100% sodium chloride) is reasonable to reduce stroke risk.
Use caution for people taking a potassium-sparing diuretic or potassium supplement and for those with known kidney disease, owing to a potential risk of hyperkalemia in this group.
Goal
Reduced risk of ischemic stroke and TIA
Adult with cigarette smoking or with other type of tobacco and/or nicotine use
All
Intervention
Treatment for smoking cessation
For people who are active cigarette smokers or users of other tobacco products, offer assistance with cessation.
Direct questioning helps classify individuals as never, past, or current smokers. Identify whether a patient is ready to quit, which is a cue to offer treatment options for smoking cessation. Ask also about other forms of tobacco, electronic nicotine delivery systems such as electronic cigarettes (e-cigarettes), and environmental tobacco smoke exposure.
For people who are active cigarette smokers, smoking cessation pharmacotherapy delivered along with behavioral counseling is recommended in preference to behavioral counseling alone.
Advise people that the long-term health benefits of using e-cigarettes in place of nicotine replacement therapy to facilitate cigarette smoking cessation are not well established.
See Smoking cessation.
Goal
Smoking, tobacco, and nicotine cessation and avoidance of environmental exposure; reduced risk of ischemic stroke and TIA
Adult with substance use problem or disorder
People who use recreational drugs (e.g., cannabis, synthetic cannabinoids, cocaine, heroin, methamphetamine), misuse alcohol or prescription medications (e.g., stimulants and opioids), or with a substance use disorder.
All
Intervention
Counseling to stop or appropriate substance use disorder treatment
Offer referral for counseling or substance use disorder treatment (e.g., pharmacologic, behavioral or multimodal) as appropriate to the nature of the substance use problem or disorder.
Screening, Brief Intervention and Referral to Treatment (SBIRT) programs have evidence of efficacy in reducing heavy drinking and illicit substance use in the short-term.
Pharmacologic treatment is an evidence-supported approach for some types of substance use disorder, including alcohol use disorder and opioid use disorder.
See Alcohol use disorder.
See Opioid use disorder.
Goal
Cessation of substance use
Cessation of substance use is recommended; observational data shows an increased risk of stroke in those with a substance use disorder, however evidence directly linking reduced use with reduction in stroke risk is lacking.
Adult with physical inactivity
All
Intervention
Counseling on recommended activity levels
Recommend that people reach physical activity targets (see goal column).
Advise people to avoid excessive time spent in sedentary behavior (characterized by low-energy expenditure while sitting, reclining, or lying while awake).
Evidence-based methods to promote physical activity include:
repeated individual counseling (minimum, 3-5 sessions), and
group meetings based on models of behavior change that typically involve goal setting, monitoring, problem solving, and feedback.
When physicians cannot provide intensive counseling themselves, brief counseling followed by referral to an exercise coach may be effective.
Goal
Reduced risk of ischemic stroke and TIA
The aim is to achieve:
at least 150 minutes of moderate-intensity physical activity;
at least 75 minutes of vigorous-intensity activity; or
an equivalent combination.
Adult with suboptimal dietary quality
All
Intervention
Advise a Mediterranean dietary pattern
Advise people that the Mediterranean diet has been shown to reduce the risk of stroke, especially when supplemented with nuts and olive oil.
Goal
Reduced risk of ischemic stroke and TIA
Adult with class II obesity or greater
Body mass index (BMI) 35-39.9 kg/m² or greater
All
Intervention
Consider a bariatric surgical procedure
Consider a bariatric surgical procedure (e.g., gastric bypass surgery or sleeve gastrectomy) to prompt weight loss to reduce the risk of cardiovascular events, including stroke.
Pharmacologic treatment for obesity may also be considered in select patients.
See Obesity in adults.
Goal
Weight loss and reduced risk of ischemic stroke, TIA and other types of atherosclerotic CVD
Adult with obstructive sleep apnea (OSA)
All
Intervention
Consider continuous positive airway pressure (CPAP)
Consider offering CPAP to people with OSA to reduce the risk of stroke.
OSA is a direct risk factor for stroke, and also increases stroke risk through its indirect effects on hypertension. There is some observational evidence to suggest that CPAP might reduce stroke risk in people with OSA.
Goal
Reduced risk of ischemic stroke and TIA
Adult with periodontal disease
All
Intervention
Promotion of good oral hygiene and regular dental care
Poor periodontal health and peridontitis are strongly associated with increased stroke risk.
Advise all people to maintain good oral hygiene and to have regular visits with a dental health professional.
Goal
Reduced risk of ischemic stroke and TIA
Adult with diabetes
Defined as: hemoglobin (Hb)A1c ≥6.5 %; or fasting plasma glucose ≥126 mg/dL; or 2-h plasma glucose from oral glucose tolerance test ≥200 mg/dL
With high cardiovascular risk or established CVD and HbA1c ≥7%
Intervention
Consider a glucagon-like peptide-1 (GLP-1) receptor agonist
Randomized controlled trials have shown that GLP-1 receptor agonists reduce stroke risk.
Direct evidence of the effect of other diabetes drugs on stroke risk reduction is lacking.
Goal
Reduced risk of ischemic stroke and TIA
Adult; with indication for lipid-lowering therapy
For example, ages 20-75 years with LDL-C >190 mg/dL (>4.9 mmol/L); or 10-year atherosclerotic CVD risk ≥20%; or 10-year atherosclerotic CVD risk ≥7.5% to <20% plus ≥1 risk enhancers
All
Intervention
Statin treatment
Treatment with a statin is recommended.
Explain to patients that treatment with a statin is associated with an overall reduction in risk of stroke in those at high cardiovascular risk; include this information within patient discussions related to the overall benefit of statins for lowering their risk of vascular events.
See Hypercholesterolemia.
Goal
Reduced risk of ischemic stroke, TIA and other types of atherosclerotic CVD
Adult with a recent myocardial infarction (MI)
Without contraindication to high-intensity statin therapy
Intervention
Consider low-dose colchicine
Consider adding low-dose colchicine to intensive statin treatment for those with a history of recent MI.
Colchicine is an anti-inflammatory medication that has been tested in a number of CVD trials, with promising results.
Goal
Reduced risk of ischemic stroke, TIA and adverse cardiovascular outcomes
Adult with autoimmune condition
With a high-risk antiphospholipid (aPL) profile
Intervention
Prophylactic low-dose aspirin
Prophylactic low-dose aspirin is recommended for those without a history of stroke and with no clinical indication for anticoagulation who have any one of the following:
Triple-positive aPL testing (lupus anticoagulant, anticardiolipin antibody, anti-β2 glycoprotein 1)
Double-positive aPL testing (any combination)
Isolated lupus anticoagulant
Isolated persistently positive anticardiolipin antibody at medium to high titer
This recommendation includes people with systemic lupus erythematosus (SLE) and without a clinical indication for anticoagulation (i.e., history of thrombosis or pregnancy complications).
Goal
Reduced risk of ischemic stroke and TIA
With SLE; with a low-risk aPL profile
Intervention
Consider prophylactic low-dose aspirin
For those without a clinical indication for anticoagulation (i.e., history of pregnancy complications or thrombosis), consider offering low-dose prophylactic aspirin.
A low-risk aPL profile is defined as:
isolated anticardiolipin antibody, or
anti-β2 glycoprotein 1 antibody at low to medium titer, particularly if transiently positive.
Less evidence exists on the use of aspirin in this group, although a reduced risk of arterial and venous thrombosis has been suggested with aspirin, based on data from 2 cohort studies.
Goal
Reduced risk of ischemic stroke and TIA
With antiphospholipid syndrome (APS); with prior unprovoked venous thrombosis
Intervention
Lifelong anticoagulation; vitamin K antagonist preferred
Lifelong anticoagulation is recommended owing to a high risk of recurrence of thrombosis.
It is reasonable to choose a vitamin K antagonist (usually warfarin) in this group in preference to aspirin or direct oral anticoagulants (DOACs), providing there are no contraindications.
Consider using a DOAC in patients not able to achieve a target international normalized ratio (INR) despite good adherence to a vitamin K antagonist (e.g., allergy or intolerance), although there is limited evidence on their safety or effectiveness in people with APS.
Goal
Reduced risk of thrombosis including ischemic stroke and TIA
A target INR of 2-3 is recommended if a vitamin K antagonist is used.
With APS; with a history of obstetric APS only
Intervention
Consider prophylactic low-dose aspirin
Consider prophylactic treatment with low-dose aspirin for nonpregnant adults with a history of obstetric APS after thorough risk/benefit evaluation.
Factors to consider as part of the decision making process include:
APL profile
Coexistent traditional cardiovascular risk factors
Intolerance or contraindication to aspirin
Goal
Reduced risk of ischemic stroke and TIA
With rheumatoid arthritis (RA)
Intervention
Consider statin treatment (if not already started)
Statin treatment may be reasonable in this group.
Some evidence supports a potential beneficial impact of statins on RA disease activity, attributable to their anti-inflammatory and immunomodulatory properties.
Goal
Reduced risk of adverse cardiovascular events, including ischemic stroke and TIA
Adult with established, stable coronary artery disease; ages <70 years and without chronic kidney disease
All
Intervention
Consider aspirin plus ticagrelor
For patients with established coronary artery disease, the use of ticagrelor in addition to background therapy with aspirin can modestly reduce risk of ischemic stroke.
This treatment is suitable only for those at low bleeding risk, as guided by an assessment of the individualized risk:benefit ratio; use of both aspirin and ticagrelor can increase the risk for bleeding events.
Note that in the absence of established coronary artery disease, the use of aspirin to prevent a first stroke is not well established.
For people ages ≥70 years with at least one additional cardiovascular risk factor, use of aspirin is not beneficial to prevent a first stroke and may be associated with harm (from bleeding).
In patients with chronic kidney disease, the use of aspirin is not effective to prevent a first stroke and may be associated with harm (from bleeding).
Goal
Reduced risk of ischemic stroke and TIA
Use of ticagrelor may be beneficial beyond 12 months, and for a period of up to 3 years, to reduce the rate of ischemic stroke.
With nonvalvular atrial fibrillation of any duration
With an annual stroke risk ≥2% (generally a CHA₂DS₂-VASc score of ≥2 in men or ≥3 in women)
Intervention
Consider oral anticoagulation (as guided by the individualized risk assessment for stroke)
Anticoagulation is generally recommended in this group.
However, risk of stroke varies among populations with the same risk score, so consider other factors related to stroke risk as part of the individualized risk assessment. An assessment of bleeding risk is key.
In individuals with nonvalvular atrial fibrillation, use a validated clinical risk score such as the CHA₂DS₂-VASc tool to guide decisions on prescription of oral anticoagulation to reduce risk for stroke. EBMcalc: CHA₂DS₂-VASc Opens in new window
It is recommended that decisions on anticoagulation are individualized in the context of shared decision-making.
Goal
Use of anticoagulation for stroke risk reduction is warranted when the benefit outweighs the harms
With heart failure with reduced ejection fraction; without atrial fibrillation or left ventricular thrombus
All
Intervention
Individualized treatment; note that anticoagulation is not indicated to prevent stroke
In patients with left ventricular systolic dysfunction (ejection fraction ≤35% to 40%) and no evidence of atrial fibrillation or left ventricular thrombus, anticoagulation is not indicated to prevent stroke and is associated with a higher bleeding risk.
Goal
Minimization of medicines-related harm (from bleeding)
Woman considering contraception
All
Intervention
Individualized contraceptive choice; for those considering combined hormonal contraception, use a lower dose of ethinyl estradiol
Evaluate risk of stroke according to individualized patient factors as well as according to the type of contraception under consideration. Risk of stroke may vary substantially between different types of hormonal contraception.
It should be noted that the overall rate of stroke in women using hormonal contraception is lower than the rate of stroke in women from pregnancy.
See Contraception.
Goal
Reduced risk of ischemic stroke and TIA
With specific stroke risk factors
Intervention
Shared decision making to determine contraceptive choice; progestin-only contraception or nonhormonal contraception may be preferred
Specific stroke risk factors include:
Age >35 years
Tobacco use
Hypertension
Migraine with aura
For those with any of the above, shared decision making is recommended to determine the best contraceptive choice.
Contraceptive choice is affected by many medical and personal factors for the patient. Shared decision making is recommended to weigh the benefits and risks of those choices.
Take into account the effectiveness of each contraceptive option and the risk of stroke associated with pregnancy. Thoughtful discussion of absolute risk is recommended.
For those with risk factors for stroke, progestin-only or nonhormonal contraception is reasonable.
For specific advice for women with migraine with aura needing contraception, see next group ('Adult with migraine [with or without aura]').
See Contraception.
Goal
To balance the risk of stroke from contraception and the risk of stroke with pregnancy
Adult with migraine (with or without aura)
All
Intervention
Evaluation and modification of vascular risk factors
Pay particular attention to risk factor screening and modification in people with migraine.
An association between migraine, particularly migraine with aura, and stroke risk has been consistently identified within observational studies.
Vascular risk factors are common in this population, even at younger ages, and contribute towards excess stroke risk.
Goal
Reduced risk of ischemic stroke and TIA
Woman with migraine with aura; contraception needed
Intervention
Recommend progestin-only or nonhormonal contraception
Advise patients with migraine with aura to avoid combined oral contraception. Use of combined hormonal contraception in those with migraine with aura is associated with increased risk for ischemic stroke.
No increased risk of stroke has been identified in individuals with migraine using progestin-only forms of contraception.
Goal
Avoid increased risk of ischemic stroke and TIA associated with combined oral contraception
Adult with endometriosis
All
Intervention
Individualized management of vascular risk factors
Asking about a history of endometriosis can be useful in evaluating stroke risk.
Young people in particular may benefit from enhanced attention to cardiovascular risk assessment and prevention strategies, although evidence is limited.
Among those with endometriosis, studies have shown a consistent increased risk of stroke (as well as other cardiovascular risk factors, e.g., hypertension and hypercholesterolemia).
Goal
Reduced risk of ischemic stroke and TIA
Adult with asymptomatic carotid artery stenosis (>70%)
All
Intervention
Intensive pharmacologic management and risk factor modification
All people should receive optimal medical management for carotid artery stenosis as well as risk factor modification; medical management is evolving and choice of treatment is guided by both multidisciplinary decision making and shared decision making between patient and clinical team.
Evidence supports the use of statin therapy for risk factor reduction in this population.
Goal
Reduced risk of ischemic stroke and TIA
At high risk of stroke despite optimal medical management
Intervention
Consider carotid revascularization
A subset of patients will remain at high risk of stroke despite optimal medical treatment; consensus is lacking as to the best course of management for these patients.
Consider whether carotid revascularization is appropriate, depending on the individualized risks versus benefit analysis, including perioperative risk.
Choice of treatment is therefore guided by multidisciplinary decision making as well as shared decision making between patient and clinical team.
Goal
Reduced risk of ischemic stroke and TIA
Adult with asymptomatic cerebral small vessel disease (SVD), including silent cerebral infarcts
All
Intervention
Careful attention to risk factor modification; consider low-dose statin
Assessment and management of modifiable risk factors is particularly important for this population (e.g., hypertension, tobacco use, dyslipidemia, and diabetes).
Consider low-dose statin therapy even for those who do not have an indication.
Goal
Reduced risk of ischemic stroke and TIA
Adult with genetic stroke syndrome
The role of genetics in stroke pathogenesis is increasingly recognized. Monogenetic conditions are the most well understood. These include Fabry disease, CADASIL, HHT, and type IV collagen (COL4A1/2) mutations, among others.
All
Intervention
Individualized approach to stroke risk modification
Although each individual genetic condition is rare, stroke risk in some can be modified with prophylactic therapy.
For patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), counseling and treatment of modifiable risk factors (e.g., smoking cessation, treatment of hypertension and other vascular risk factors) is particularly important.
Variable expression inherent in many genetic disorders makes uniform recommendations for stroke prevention challenging.
Goal
Reduced risk of ischemic stroke and TIA
With hereditary hemorrhagic telangiectasia (HHT); with pulmonary arteriovenous malformation (PAVM) identified
Intervention
Multidisciplinary evaluation to manage stroke risk
It is recommended that a multidisciplinary team with expertise in HHT weigh up the risks and benefits of intervention for patients with PAVMs.
As a minimum, this consists of specialists in:
Pulmonology
Interventional radiology
Neurology/neurosurgery
PAVMs are present in nearly half of patients with HHT and are associated with embolic complications, including ischemic stroke and brain abscesses.
Goal
Reduced risk of ischemic stroke and TIA
Adult with previous specific adverse pregnancy outcomes (APOs)
Includes: hypertensive disorder of pregnancy, preterm birth, gestational diabetes, recurrent pregnancy loss, small for gestational age infant, placental abruption, miscarriage, or stillbirth.
All
Intervention
Individualized management of vascular risk factors
It is recommended that obstetrician-gynecologists and other primary care clinicians screen parous women for a history of APOs and discuss the increased risk of stroke with these patients, who are often unaware of their risk.
Mounting data support that those who experience APOs have increased risk and earlier onset of cerebrovascular disease.
These discussions may also help patients make informed decisions about future pregnancies.
Pay particular attention to modifiable vascular risk factors. Even young adults with a history of APOs have an increased risk of developing chronic hypertension as soon as 2 years after the index pregnancy; early diagnosis and treatment is key. Women who have experienced preeclampsia and gestational hypertension are at particularly high risk of chronic hypertension and stroke later in life.
Goal
Reduced risk of ischemic stroke and TIA
Woman with menopause
Considering oral estrogen-based therapy for management of menopausal symptoms
Intervention
Careful risk factor assessment and evaluation
In women ages ≥60 years, more than 10 years after natural menopause, or at elevated risk for CVD or stroke, oral estrogen-containing hormonal treatment to manage vasomotor symptoms of menopause is associated with an excess risk of stroke. It is recommended that clinicians use shared decision making when selecting hormonal therapy and weigh this risk against clinical benefits in those at excess stroke risk.
It is important to note that topical estrogen treatments are not associated with stroke risk.
See Menopause.
Goal
Reduced risk of ischemic stroke and TIA
With premature ovarian failure or early menopause
Intervention
Individualized management of vascular risk factors
Premature ovarian failure is defined as menopause before age 40 years. Early menopause is defined as menopause before age 45 years.
Evaluation and modification of vascular risk factors are recommended in these groups owing to an increased risk of stroke.
In particular, earlier changes in lipids and BP have been noted compared to those with later onset of menopause; monitoring and treatment of lipids and BP (as well as other CVD risk factors) is recommended during menopausal transition.
The ACC/AHA 2018 guideline on cholesterol management included premature menopause as a risk-enhancing factor to be considered in cholesterol management decisions.
Premature ovarian failure and early menopause may be due to primary ovarian insufficiency or secondary to medical treatment (medical or surgical); the type of menopause does not appear to modify the association with stroke.
Data are lacking on whether hormone replacement therapy, at least until the average age of menopause, may modify this risk.
Goal
Reduced risk of ischemic stroke and TIA
Transgender woman or gender diverse person taking estrogens for gender affirmation
All
Intervention
Individualized management of vascular risk factors
It is recommended that clinicians evaluate and address risk factors in transfeminine people using gender-affirming hormone therapy (e.g., tobacco use, hypertension) owing to a potential increased risk of stroke in this population.
Transgender and gender diverse people experience disparate access to and outcomes within health care, including stroke.
Goal
Reduced risk of ischemic stroke and TIA
Man with hypogonadism; with appropriate indication for testosterone therapy
All
Intervention
Advise that initiation or continuation of testosterone therapy is reasonable
In men ages 45 to 80 years with confirmed hypogonadism who are considering testosterone therapy, initiation or continuation of testosterone replacement therapy is reasonable and does not increase the risk of stroke.
The potential increased risk of stroke in men with confirmed hypogonadism using exogenous testosterone has been debated for several years; however, patients may be reassured that recent data suggest that initiation or continuation of transdermal testosterone in people with appropriate indications does not increase the risk of stroke.
See Hypogonadism in men.
Goal
Favorable balance of risk versus benefits of treatment with testosterone
Secondary prevention
The American Heart Association/American Stroke Association (AHA/ASA) have published recommendations for the secondary prevention of ischemic stroke.[113]
Secondary prevention measures should be started for all patients as soon as possible after the diagnosis is confirmed.
Patients should be advised on lifestyle measures including recommendations to:[113]
Exercise regularly
Maintain a healthy diet
Manage weight
Reduce alcohol consumption
Stop smoking.
See Management approach for more detail on the recommendations below.
Anticoagulation for stroke patients with atrial fibrillation (AF)
The AHA/ASA guidelines recommend starting oral anticoagulation 4-14 days after stroke symptom onset.[135]
In patients with nonvalvular AF and stroke or TIA, oral anticoagulation is recommended to reduce the risk of recurrent stroke, regardless of whether the AF pattern is paroxysmal, persistent, or permanent.[113]
Direct-acting oral anticoagulants (DOACs) such as apixaban, dabigatran, edoxaban, or rivaroxaban are recommended over warfarin in patients with stroke or TIA and AF who do not have moderate to severe mitral stenosis or a mechanical heart valve.[113]
Warfarin remains the choice for thromboembolic prevention in patients with mechanical heart valves.[112][113] The international normalized ratio (INR) range for patients on warfarin is 2.0 to 3.0.[113][228] A validated scoring system should be used to assess the bleeding risk of the patient; if high, the patient should be followed up more closely.[229][324] See New-onset atrial fibrillation.
See Management approach for more information.
Antiplatelet therapy for patients with stroke without AF
For patients with noncardioembolic ischemic stroke or TIA, aspirin, clopidogrel, or the combination of aspirin and extended-release dipyridamole is indicated for secondary prevention of ischemic stroke.[113]
In patients with recent minor (NIHSS score ≤3) noncardioembolic ischemic stroke or 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 21-90 days, followed by single antiplatelet therapy, to reduce the risk of recurrent ischemic stroke.[113]
Ticagrelor is approved by the Food and Drug Administration to reduce the risk of stroke in patients with acute ischemic stroke or high-risk TIA. Ticagrelor reversibly binds and inhibits the P2Y12 receptor on platelets. 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 and aspirin reduced the risk of disabling stroke or death within 30 days (4.0% vs. 4.7%).[191] Severe bleeding was more frequent with ticagrelor plus aspirin than with aspirin alone (0.5% vs. 0.1%), including intracranial hemorrhage (0.4% vs. 0.1%).[191] 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.
Stroke or TIA with stenosis of a major intracranial artery
In patients with a stroke or TIA caused by 50% to 99% stenosis of a major intracranial artery, aspirin is recommended in preference to warfarin to reduce the risk of recurrent ischemic stroke and vascular death.[24][113]
In patients with recent stroke or TIA (within 30 days) attributable to severe stenosis (70% to 99%) of a major intracranial artery, the addition of clopidogrel to aspirin for up to 90 days is recommended to further reduce recurrent stroke risk in patients who have low risk of hemorrhagic transformation.[24][113]
In patients with recent (within 24 hours) minor stroke or high-risk TIA and concomitant ipsilateral >30% stenosis of a major intracranial artery, the addition of ticagrelor to aspirin for up to 30 days might be considered to further reduce recurrent stroke risk.[113]
In patients with stroke or TIA attributable to 50% to 99% stenosis of a major intracranial artery, the addition of cilostazol to aspirin or clopidogrel might be considered to reduce recurrent stroke risk.[113]
Carotid artery endarterectomy (CEA) and carotid artery stenting (CAS)
In patients with symptomatic carotid stenosis (i.e., TIA or nondisabling stroke) within the past 6 months and ipsilateral severe (70% to 99%) carotid artery stenosis, CEA is recommended to reduce the risk of future stroke, provided that perioperative morbidity and mortality risk is estimated to be <6%.[113]
In patients younger than 68 years and with symptomatic carotid stenosis (i.e., TIA or nondisabling stroke), CAS is preferred over CEA if the degree of stenosis is between 50% and 69% (as determined by digital subtraction angiography). This is appropriate only if perioperative risk of morbidity and mortality is <6%. CEA or CAS is beneficial for patients with 70% to 99% stenosis without near-occlusion. No evidence of benefit has been found in patients with a stenosis of <50% or near-occlusion.[46][47][231]
In patients older than 68 years and with recent TIA or ischemic stroke and ipsilateral moderate (50% to 69%) carotid stenosis (as documented by catheter-based imaging or noninvasive imaging), CEA is recommended to reduce the risk of future stroke, provided the perioperative morbidity and mortality risk is <6%. Patient-specific factors such as age, sex, and comorbidities will also affect the suitability of CEA.[113]
Patent foramen ovale
PFO closure (with antiplatelet therapy), antiplatelet therapy alone, or anticoagulants alone are options for the secondary prevention of stroke in patients with cryptogenic ischemic stroke secondary to PFO.[234] Antiplatelet options include aspirin or clopidogrel.[235]
The approach chosen depends on the risk of paradoxical embolism, age, patient preference, and vascular risk factors.
Drugs used for secondary prevention should be reviewed. Some patients may have been started on these drugs at diagnosis.
Antiplatelet therapy
For patients with noncardioembolic ischemic stroke or TIA, guidelines from the AHA/ASA recommend aspirin, clopidogrel, or the combination of aspirin plus extended-release dipyridamole for secondary prevention of ischemic stroke.[113] In patients with recent minor (NIHSS score ≤3) noncardioembolic ischemic stroke or high-risk TIA (ABCD2 score ≥4), 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 21-90 days, followed by single antiplatelet therapy, to reduce the risk of recurrent ischemic stroke.[113][135][186][187]
In 2020, the Food and Drug Administration (FDA) in the US approved the dual antiplatelet regimen of aspirin and ticagrelor to reduce the risk for stroke in patients with acute ischemic stroke with a NIHSS score of ≤5 or high-risk TIA. 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 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.
Some guidelines recommend CYP2C19 genotype testing to assess if clopidogrel is a suitable antiplatelet drug for people who have just had an ischemic stroke or a TIA.[192] When interpreting test results, the prevalence of different CYP2C19 genotypes may vary between ethnic groups should be taken into account.
Antihypertensives
One systematic review found that blood pressure lowering treatment reduced the risk of recurrent stroke in people with stroke or TIA. Evidence was derived primarily from trials studying an ACE inhibitor or a diuretic.[325] In patients with hypertension who experience a stroke or TIA, treatment with a thiazide diuretic, ACE inhibitor, or angiotensin-II receptor antagonist is useful for lowering blood pressure and reducing recurrent stroke risk.[113] An office blood pressure goal of <130/80 mmHg is recommended for most patients to reduce the risk of recurrent stroke and vascular events. Drug regimens should be individualized to take into account patient comorbidities, agent pharmacological class, and patient preference.[113]
The American Academy of Neurology recommends a long-term blood pressure target of <140/90 mmHg in patients with symptomatic intracranial atherosclerotic arterial stenosis.[24] Drug regimens should be individualized to take into account patient comorbidities, agent pharmacological class, and patient preference.[24][113]
Anticoagulants
Should be started in people with stroke and paroxysmal, persistent, or permanent atrial fibrillation or atrial flutter once intracranial bleeding and other contraindications (such as uncontrolled hypertension) are excluded.
Lipid-lowering treatments
Statin therapy with intensive lipid-lowering effects is recommended for patients with ischemic stroke or TIA, to lower the risk of stroke and cardiovascular events.[113][246] The rate of recurrent cardiovascular events or stroke is lower in patients whose LDL is controlled to <70 mg/dL compared with those with LDL between 90 and 110 mg/dL.[24][247] Monitoring of liver enzymes is recommended for patients taking statins. Caution should be exercised when prescribing high-intensity statin to patients with a history of intracerebral hemorrhage.
In patients with ischemic stroke with no known coronary heart disease, no major cardiac sources of embolism, and LDL cholesterol (LDL-C) >100 mg/dL, atorvastatin is indicated to reduce risk of stroke recurrence.[113]
In patients with ischemic stroke or TIA and atherosclerotic disease (intracranial, carotid, aortic, or coronary), lipid-lowering therapy with a statin and also ezetimibe, if needed, to a goal LDL-C of <70 mg/dL is recommended to reduce the risk of major cardiovascular events.[113]
In patients with ischemic stroke who are very high risk (defined as stroke plus another major atherosclerotic CVD or stroke plus multiple high-risk conditions), are taking maximally tolerated statin and ezetimibe therapy and still have an LDL-C >70 mg/dL, it is reasonable to treat with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy to prevent atherosclerotic CVD events.[113] BMJ: PCSK9 inhibitors and ezetimibe for the reduction of cardiovascular events Opens in new window
In patients with stroke or TIA and hyperlipidemia, adherence to changes in lifestyle and the effects of LDL-C-lowering drugs should be assessed by measurement of fasting lipids and appropriate safety indicators 4-12 weeks after statin initiation or dose adjustment and every 3-12 months thereafter, based on need to assess adherence or safety.[113]
In patients with ischemic stroke or TIA, with fasting triglycerides 135 to 499 mg/dL and LDL-C of 41 to 100 mg/dL, on moderate- or high-intensity statin therapy, with HbA1c <10%, and with no history of pancreatitis, atrial fibrillation, or severe heart failure, treatment with icosapent ethyl is reasonable to reduce risk of recurrent stroke.[113][326]
In patients with severe hypertriglyceridemia (i.e., fasting triglycerides ≥500 mg/dL [≥5.7 mmol/L]), it is reasonable to identify and address causes of hypertriglyceridemia and, if triglycerides are persistently elevated or increasing, to further reduce triglycerides in order to lower the risk of atherosclerotic CVD events by implementation of a very low-fat diet, avoidance of refined carbohydrates and alcohol, consumption of omega-3 fatty acids, and, if necessary to prevent acute pancreatitis, fibrate therapy.[113]
Additional secondary prevention measures may be necessary depending on stroke risk factors and associated diseases discovered during investigations for the cause of stroke.[113][327]
Sleep studies should be considered for stroke patients because sleep apnea is common among this subgroup.[262] In patients with an ischemic stroke or TIA and obstructive sleep apnea, treatment with positive airway pressure (e.g., continuous positive airway pressure [CPAP]) may be beneficial for improved sleep apnea, blood pressure, sleepiness, and other apnea-related outcomes.[113]
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