Managing & Preventing Different Strokes

The recognition of stroke symptoms and the rapid delivery of acute treatment have evolved at a rapid pace over the past 15 years. The prevention of stroke recurrence also has improved.

Many important factors have contributed to current understanding of stroke. The definition of transient ischemic attack (TIA) has been revised and now excludes the patient whose acute neuroimaging findings reveal ischemia even if clinical symptoms have resolved. This change has shifted some formerly classified TIA patients into the category of ischemic stroke.

An ischemic stroke is the result of neuronal death due to lack of oxygen, a deficit that produces focal brain injury. This event is accompanied by tissue changes consistent with an infarction that can be identified with neuroimaging of the brain. Strokes are usually accompanied by symptoms, but they also may occur without producing clinical findings and be considered clinically silent.

Prevalence & Incidence

Stroke affects approximately 795,000 Americans each year, and approximately 6.4 million stroke survivors are now living in the United States.1 Progress has been made in reducing stroke mortality, and it recently dipped to the fourth spot among leading causes of death in the United States. However, stroke is the leading cause of disability: 20% of survivors still require institutional care after three months and 15% to 30% experience permanent disability.1 Stroke is a life-changing event that also affects the patient’s family members and caregivers.

Both acute and chronic conditions may result in cerebral ischemia or stroke. Acute events that can lead to stroke include cardiac arrest, drowning, strangulation, asphyxiation, choking, carbon monoxide poisoning, and closed head injury. More commonly, the etiology of stroke is related to chronic medical conditions including large artery atherosclerosis, atrial fibrillation, left ventricular dysfunction, mechanical cardiac valves, diabetes, hypertension and hyperlipidemia. Regardless of cause, prompt recognition of symptoms and urgent medical attention are necessary for thrombolytic therapy to be considered and provided.

Acute Assessment & Treatment

Unlike 15 years ago, a treatment for stroke now exists, and research shows it improves outcomes by reducing post-stroke disability. Time is the most important factor in the initiation of treatment, and this has prompted increased education and awareness campaigns for the public and emergency services providers about the signs and symptoms of stroke.

The arrival of a stroke patient in the emergency department (ED) must be viewed as a true emergency, and the urgent care of such patients should receive priority. On arrival to the ED, identification of the patient with a potential stroke should prompt the collection of several important data points:

  • time the patient was last known to be neurologically normal
  • detailed neurological exam or use of National Institutes of Health Stroke Scale (NIHSS; Table 1)
  • serum glucose level
  • medical history
  • current medications.

Archive ImageAPriority diagnostic testing is also necessary. The ED staff should obtain a stat noncontrast CT scan of the brain and perform laboratory assessment of glucose, complete blood count, prothrombin time, partial thromboplastin time and international normalized ratio (INR) levels. These results will help rule out potential contraindications and risks associated with the use of IV thrombolytic therapy. The first priority is to determine eligibility for IV administration of tissue plasminogen activator (tPA); this process is most effective and streamlined with the use of protocols. Table 2 lists criteria used to determine patient eligibility for IV tPA administration.

IV tPA is the first and only therapy approved for the treatment of acute ischemic stroke. It was cleared by the FDA in 1996, after the completion of the National Institute of Neurological Disorders and Stroke rtPA (NINDS) trial.2 tPA is approved for use in patients who present to the ED within 3 hours of symptom onset and have a persistent neurological deficit consistent with stroke and who meet the inclusion criteria. Rapid diagnostic testing is essential to making decisions about tPA administration. The goals are “Door to CT” in less than 25 minutes and “Door to Treatment” in less than 60 minutes.

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Figure 1. This MRI using diffusion-weighted imaging shows white hyperintensity in the left thalamus, representing acute ischemic stroke. All figures courtesy the author

IV tPA dosing is based on weight; therapy is initiated with a 10% bolus followed by a 1-hour infusion of the remaining dose.2 Patients who receive IV tPA require admission to the intensive care unit (ICU), where staff members can provide frequent vital sign assessment and perform recommended neurologic examinations. Potential complications of IV tPA include intracranial bleeding and systemic bleeding.2 Blood pressure management for the first 24 hours is necessary.2

Interventional therapy in acute ischemic stroke is now possible as a result of the FDA’s approval of the Merci Retriever3 and the Penumbra System.4 These mechanical embolectomy devices are inserted into the artery through a base catheter that feeds up to the occlusion or clot. They are then deployed or activated to mechanically remove the clot from the artery.

The Merci Retriever has a corkscrew-like tip with filamentous strands to help retrieve the clot. The Penumbra device uses external suction and a macerating catheter to penetrate the clot. The goal is to break the clot into smaller pieces and then apply suction to remove it from the artery lumen. Both devices have an extended time window for use that can sup up to eight hours after onset of stroke symptoms. These interventional approaches are indicated for patients who do not qualify for IV tPA or do not undergo vessel recanalization after IV tPA administration. Mechanical embolectomy devices may be used in conjunction with small doses of intra-arterial tPA or in combination with angioplasty and/or stenting. Additional devices are in clinical trials.

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Figure 2. This MRI using fluid-attenuated inversion recovery shows white hyperintensities in the periventricular areas, representing chronic small vessel ischemic disease.

Advances in neuroimaging technology for computed tomography (CT) and magnetic resonance imaging (MRI) now provide more detailed information about vessel patency and tissue viability. This technology helps the stroke treatment team better determine proximal and distal artery patency. It also helps them differentiate infarcted core tissue from at-risk penumbral tissue.

Current recommendations for patients who present with an acute onset of neurological symptoms are to obtain a stat noncontrast CT scan to rule out hemorrhage or evidence of early ischemia.5 Adjunctive imaging using a contrast agent provides information about the patency of vessels. CT angiography (CTA) is thus often obtained when the initial CT scan is performed in the ED. MRI scanners are now available in many acute care settings. Magnetic resonance angiography (MRA) and magnet resonance perfusion are also valuable in determining large artery stenosis or occlusion and in quantifying the volume of ischemic brain tissue.

Maintenance of cerebral perfusion to limit brain tissue ischemia is the primary goal in the acute period after ischemic stroke. Neurologic recovery may occur in the early stages after stroke, when the ischemic brain tissue is reperfused prior to tissue infarction. Research shows that close monitoring and specialty nursing care delivered in stroke units can improve outcomes in stroke patients. Patients who have received IV thrombolysis or intra-arterial intervention should be admitted to an ICU, where continuous cardiac monitoring, detailed neurologic examinations and high-level nursing care can be provided. Patients who experience large strokes or do not receive thrombolytics are at risk for neurologic or hemodynamic decline and should receive treatment in a critical care environment.

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Figure 3.This MRI using T2 mean gradient sequences shows a dark spot in the left hemisphere, representing a microhemorrhage.

Secondary Stroke Prevention

Therapy to prevent stroke after a clinical event (TIA or stroke) varies and is individualized depending on the results of the diagnostic evaluation and presumed etiology. Following a stroke, all patients should undergo a diagnostic evaluation to determine its cause. Within the stroke specialty, the etiology is categorized using the TOAST criteria, a reference to a study titled Trial of Org 10172 in Acute Stroke Treatment.6 In this classification system, strokes are identified by cause: cardiac embolism (CE); large artery atherosclerosis (LAA); small artery occlusion (SAO); acute stroke of other determined etiology (ASODE); or stroke of undetermined etiology (SUE).

Albers et al. report the breakdown by category as follows: 20% of ischemic strokes are caused by LAA, 20% are caused by CE, 25% are caused by SAO, and 30% are SUE.7 The remaining 5% of strokes can be categorized as ASODE.7 These percentages may vary slightly according to geographic area.

A comprehensive diagnostic evaluation is necessary after stroke to determine cause and to guide medical or surgical therapy to prevent recurrence. The recommended diagnostic workup after stroke includes the following:8

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Figure 4.This MRA scan shows an intracranial view of the carotid arteries, middle cerebral arteries (MCA) and right MCA signal loss, representing stenosis.

  • Vessel imaging of intracranial and extracranial vasculature with MRA of the head and neck or CTA of the head and neck. Carotid Doppler scanning provides information on the velocity of flow in the carotid system extracranially and limited information about extracranial posterior circulation and intracranial vessel status.
  • Repeat brain imaging is recommended 24 hours after IV tPA administration or intervention to assess for stroke size and the presence of hemorrhage. A repeat CT scan is obtained if the patient is unable to undergo MRI. MRI of the brain provides more detailed information with diffusion-weighted imaging (acute stroke signal), fluid attenuation inversion recovery (older stroke signal) and T2 sequences (presence of hemorrhage or hemosiderin representing remote hemorrhage).
  • Electrocardiography and prolonged cardiac monitoring are ordered to evaluate for atrial fibrillation, atrial flutter and to rule out other cardiac arrhythmias.
  • Transthoracic echocardiogram is performed to evaluate cardiac and valvular function and to rule out intracardiac shunt.
  • A fasting lipid panel is drawn to assess for hyperlipidemia.
  • Hemoglobin A1c is determined to assess for diabetes.

Secondary Prevention Strategies

The secondary prevention of stroke incorporates strategies to reduce the risk of stroke recurrence after a stroke or TIA. Management strategies include risk factor modification, the use of antithrombolytic or anticoagulant drugs, surgery, and endovascular treatments. These strategies are outlined in the sections that follow.

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Anticoagulation/antiplatelet treatment

Anticoagulant therapy may be warranted if a cardiac source of stroke is determined. This includes atrial fibrillation, prosthetic mechanical valve and severely reduced left ventricular (LV) function with or without LV thrombus. Anticoagulation is effective in the prevention of stroke.8 Close medical monitoring of INR, with a goal of 2.0 to 3.0, is recommended for stroke prevention in patients with atrial fibrillation.8

For patients with mechanical prosthetic cardiac valves, warfarin is recommended with a target INR of 3.0 to prevent embolic stroke.8 Bioprosthetic heart valves are not considered a significant risk factor for an embolic ischemic stroke and unless cardiac imaging suggests otherwise, aspirin therapy is typically prescribed.

Anticoagulation options to prevent recurrent ischemia vary depending on the presence of stroke and stability after ischemic stroke. Short-term anticoagulation can be accomplished with IV heparin or weight-based subcutaneous low molecular weight heparinoids. These agents are often used in the initial stages after stroke, when introducing anticoagulant agents and if bridging is necessary while anticoagulation must be interrupted. The benefit of short-term anticoagulation in the acute stroke patient is that the effects can be easily reversed and it has a shorter half-life.

Long-term anticoagulation to reduce stroke recurrence risk may be accomplished with administration of daily oral warfarin, dabigatran or rivaroxaban. Warfarin dosing and response must be monitored with serum analysis to achieve target INR values. Dabigatran is a newer anticoagulant agent that works as a direct thrombin inhibitor. It was approved after the RE-LY trial demonstrated safety and efficacy compared to warfarin. Dabigatran is an oral medication that is administered twice daily and requires no serum monitoring. Dosage adjustments are necessary in patients with renal impairment.9 Rivaroxaban is a factor Xa inhibitor that was recently compared to warfarin in the ROCKET AF trial.10 The results showed that the drug is not inferior to warfarin, and rivaroxaban now has an FDA-approved indication for the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. An even newer drug, apixaban, was recently compared to warfarin and found to be superior in stroke prevention for patients with atrial fibrillation.11 At press time in May 2012, the FDA had not approved apixaban.

Aspirin use for primary stroke prevention in the setting of atrial fibrillation is not well supported. It may be used as an alternative in patients who are deemed high risk, or when anticoagulation therapy cannot be safely administered.8

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The stroke literature contains ample documentation that aspirin therapy prevents recurrent stroke in patients with recent TIA or strokes of nonembolic etiology. The dosage range is wide and sups from 50 mg/day to 1,500 mg/day, but the most commonly used doses are 81mg/day and 325 mg/day. The recognized potential risks of aspirin therapy include bleeding and gastrointestinal upset or hemorrhage.

Dipyridamole combined with aspirin is an oral agent approved for secondary stroke prevention in non-cardioembolic stroke. Dipyridamole acts by inhibiting phosphodiesterase, and it supplements prostacyclin-related platelet aggregation inhibition. The recommended dosing is twice daily, a regimen that provides 25 mg aspirin and 200 mg dipyridimole per dose.12 The most commonly reported side effects are headache and gastrointestinal upset.

Clopidogrel is a platelet receptor antagonist also approved for secondary stroke prevention. It is dosed once daily at 75 mg and has a similar safety profile to aspirin alone.13 A potential medication interaction exists with medications that are metabolized via the CYP2C14 hepatic track. Proton pump inhibitors are included in this category and can reduce the effectiveness of clopidogrel. Consideration of alternate medication agents for the treatment of heartburn or gastroesophageal reflux is recommended. Clopidogrel is an acceptable alternative in patients who have an aspirin allergy.

The co-administration of clopidogrel and aspirin does not reduce recurrent stroke, but it does increase the risk of major hemorrhage.14 The only current recommendation for combination antiplatelet therapy with aspirin and clopidogrel is in patients who have undergone carotid stenting.15 The combined effects of these two antiplatelet agents are beneficial in reducing in-stent thrombosis, and therapy is generally continued for 3 months after stenting. After this initial period and after carotid ultrasound is performed to validate stent patency, single antiplatelet therapy is often prescribed.

Hypertension treatment

The American Heart Association recently published a statement on the primary prevention of stroke and recommended regular blood pressure screening and medication therapy when systolic blood pressure (SBP) exceeds 140 mm Hg or diastolic blood pressure (DBP) exceeds 90 mm Hg. The JNC 7 recommendations divide hypertension into three categories: prehypertension, Stage 1 hypertension and Stage 2 hypertension.16

In patients with prehypertension (defined as SBP 120 mm Hg to 139 mm Hg or DBP 80 mm Hg to 89 mm Hg), regular monitoring and education about lifestyle modifications to reduce risk of progression to stage 1 or 2 hypertension and prevention of cardiovascular disease is recommended.

Stage 1 hypertension is defined as SBP 140 mm Hg to 159 mm Hg or DBP 90 mm Hg to 99 mm Hg, and Stage 2 hypertension is defined as SBP > 160 mm Hg or DBP > 100 mm Hg. In both stage 1 and 2 hypertension, medication therapy is recommended in addition to lifestyle modifications and regular monitoring. Most patients require two antihypertensive medications to achieve desired blood pressure goals.17 When hypertension coexists with diabetes, more aggressive blood pressure lowering can reduce ischemic stroke risk.

Diabetes management

Nearly 8% of the adult population in the United States has diabetes mellitus.18 Diabetes increases the risk of first stroke, but appropriate identification and effective glucose management can reduce the risk of recurrent stroke.8 Current recommendations for primary prevention of stroke in patients with diabetes are coupled with those for hypertension and hyperlipidemia. A patient who is diabetic is likely to also have additional risk factors for stroke, including hypertension and hyperlipidemia, and they should be aggressively co-managed.

Lipid management

Elevations in serum cholesterol and its components are directly related to increased vascular disease risk. This is true for coronary artery disease as well as ischemic stroke.

Statins in combination with dietary change, weight management and physical activity can reduce total cholesterol and low-density lipoprotein cholesterol (LDL-C). Current recommendations for LDL-C in patients with TIA or ischemic stroke and evidence of atherosclerosis are to achieve and maintain LDL-C less than 100 mg/dL.8

The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial was designed to evaluate the benefit of cholesterol-lowering in stroke patients without evidence of CHD. The study found that by introducing atorvastatin, patients who accomplished greater than 50% reduction in LDL-C could reduce their stroke risk by approximately 35%.19

Lifestyle modification

Lifestyle modifications including smoking cessation are indicated for appropriate patients. Individualized education about diet, nutrition and exercise are also necessary to reduce the risk for recurrent stroke in patients with dyslipidemia.

Carotid endarterectomy or stenting

In the presence of carotid stenosis, intervention to revascularize cerebral circulation is recommended when carotid atherosclerotic plaque measures 70% stenosis and active neurologic sequelae referable to that vascular territory is evident.

The recently completed Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) compared carotid endarterectomy to carotid artery stenting in patients with 70% carotid stenosis and a clinical stroke or TIA in the appropriate vascular territory.20 The results showed no difference in mortality or morbidity in terms of myocardial infarction or recurrent stroke rates between the two interventional groups.20 This trial examined treatment in patients with symptomatic carotid stenosis. Symptomatic stenosis is defined as a clinical symptom consistent with a TIA, nondisabling stroke or transient monocular blindness confirmed by diagnostic arterial testing that reveals ipsilateral stenosis of the internal carotid artery. The safety and benefit of stroke prevention treatment in patients with asymptomatic high-grade carotid stenosis will be studied next.

Today’s Challenges

Advances in the recognition, diagnosis and treatment of stroke have improved patient outcomes. We need continued national efforts to increase patient awareness of stroke symptoms. We need to ensure that urgent assessment of possible stroke symptoms is performed in all settings. And we need to continue working to achieve improved awareness and control of the recognized risk factors for stroke.

References

1. Lloyd-Jones D, et al. Heart Disease and stroke statistics – 2010 update: a report from the American Heart Association. Circulation. 2010;121(7):e46-e215.

2. The National Institute of Neurological Disorders and Stroke rtPA Stroke study Group: Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995:333(24):1581-1587.

3. Smith WS, et al. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke. 2005;36(7):1432-1438.

4. Bose A, et al; the Penumbra Phase 1 Stroke Trial Investigators. The Penumbra System: a mechanical device for the treatment of acute stroke due to thromboembolism. AJNR. 2008;29(7):1409-1413.

5. Latchaw RE, et al; American Heart Association Council on Cardiovascular Radiology and Intervention, Stroke Council, and the Interdisciplinary Council on Peripheral Vascular Disease. Recommendations for imaging of acute ischemic stroke. Stroke. 2009;40(11):3646-3678.

6. Adams HP, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. Stroke. 1993;24(1):35-41.

7. Albers GW, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: the Seventh ACCP conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(Suppl 3):483s-512s.

8. Furie KL, et al. Guidelines for the prevention of stroke in patients with stroke or TIA: a guideline for healthcare professionals from the AHA/ASA. Stroke. 2011;42(1):227-276.

9. Connolly SJ, et al; RE-LY Steering Committee and Investigators. N Engl J Med. 2009;361(12):1139-1151.

10. Patel MR, et al. and the ROCKET AF Steering Committee. Rivaroxaban versus warfarin in nonvalvular atrial fribrillation. N Engl J Med. 2011;365:883-891.

11. Granger CB, et al; ARISTOTLE Committees and investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981-992.

12. Diener HC, et al. European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996;143(1-2):1-13.

13. A randomized, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet.1996;348(9038):1329-1339.

14. Diener HC, et al; MATCH investigators. Aspirin and clopidogrel compared to clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomized, double-blind, placebo controlled trial. Lancet. 2004;364(9431):331-337.

15. Bhatt DL, et al. Dual antiplatelet therapy with clopidogrel and aspirin after carotid artery stenting. J Invasive Cardiol. 2001;13(12):767-771.

16. Chobanian AV, et al. The seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA. 2003;289(19):2560-2572.

17. US Department of Health and Human Services. National Institutes of Health, National Heart, Lung and Blood Institute, National High Blood Pressure Education Program. Reference card from the seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. http://www.nhlbi.nih.gov/guidelines/hypertension/phycard.pdf. Accessed May 18, 2012.

18. American Diabetes Association. Standards of medical care in diabetes – 2010. Diabetes Care. 2010;33(Suppl 1):s11-s61.

19. Amarenco P, et al. Effects of intense low density lipoprotein cholesterol reduction in patients with stroke or transient ischemic attack: the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Stroke. 2007;38(12):3198-3204.

20. Brott TG, et al for the CREST Investigators. 2010. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med. 2010;363(1):11-23.

Lori M. Massaro is an acute care nurse practitioner who is the clinical supervisor at the University of Pittsburgh Medical Center Stroke Institute and a member of the adjunct faculty for the University of Pittsburgh School of Nursing.

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