Heart Disease and Stroke in Canada 1997

8. Stroke: Current Management and Prevention Strategies

In this section, the current trends of stroke mortality and disability will be examined. As well, the mechanisms and management of acute stroke will be reviewed. To conclude, a section on prevention, primary, secondary, and tertiary, will be presented.

Trends in Stroke

It is well established that stroke is a major contributor to mortality and morbidity worldwide ^112-117 . In Canada and other developed nations, the mortality due to stroke is declining ^{113, 114, 117-121} . Today, Canada enjoys one of the lowest rates of death due to stroke ^112,115 however, morbidity and associated hospitalization remains unacceptably high ¹¹⁴.

In Canada, the mortality rate due to stroke has declined approximately 50% over the past 20 years to the current level of 50 deaths per 100,000 Canadians per year, which represents 7% of all-cause mortality ^112,115 . The decline in stroke-related mortality has been attributed both to improved survival following stroke ^122,123 and to decreased incidence ^124-126 . Both risk factor management and health promotion have had a role to play in the declining incidence. Population-based public health strategies targeted towards smoking cessation, diet, exercise and weight control ^127,128 have contributed substantially as has medical management of hypertension, hyperlipidemia, diabetes, and cardiovascular disease. This combined effort has increased the public's awareness of the risk factors for cardiovascular and cerebrovascular disease.

However, despite this positive portrait, there is evidence that the rate of decline in incidence of stroke has reached a plateau ^122,129-132 . Reasons for this are still unclear ¹³⁰ . It may be that advances in diagnostic procedures have improved the detection of strokes. It is also hypothesized that current advances in the treatment of cardiovascular disease which have resulted in improved survival have placed a greater proportion of the population at risk to develop recurrent cerebrovascular disease ¹³⁰.

It is believed, however, that strokes are becoming, if not less frequent, less devastating. Unfortunately, there is no systematic way in Canada for this important information to be documented. However, there is indirect evidence of this effect over time, as a greater proportion of patients have been able to return home after a stroke. In fact, each year over a ten-year period from 1982-1991, 1,000 more persons in Canada were affected by stroke. The numbers of people dying from stroke or being so severely disabled that they required permanent institutional care, however, did not increase at the same rate. In fact, the case-fatality rate for stroke declined over the period. The major gain appears to be in the number of persons able to return home. Hospital discharge patterns provide a proxy measure for severity of stroke, thus, without a mechanism to collect data on stroke systematically in Canada, such conclusions are speculative.

Mechanisms and Management of Acute Stroke

Due to enhanced awareness of the problem of stroke and intensive research, the mechanisms of neuronal injury during cerebral ischemia are becoming better understood ¹³³ . While it has been known for over fifty years that brain cells die within minutes after the onset of ischemia, it has only recently become apparent that neuronal damage does not proceed uniformly across vascular territories. In infarction in the middle cerebral artery (MCA) distribution, for example, the most distal region in the vascular territory with reduced blood flow shows signs of damage very early after an acute arterial occlusion ^134,135 . Adjacent regions with collateral blood flow may survive for several hours before permanent damage becomes evident ^136,137 . This knowledge offers hope for therapeutic intervention to improve outcome ¹³⁸.

One key to successful outcome after an acute stroke lies in rapid evaluation, localization of the lesion and definition of the mechanism of the disease process. Patients admitted to an acute stroke care unit do better than individuals with similar lesions admitted to a general medical service. In addition to a shortened hospital stay, such patients also have a better long-term prognosis ^139,140 . Appropriate evaluation requires an adequate knowledge of the anatomy of the cerebral vasculature, potential mechanisms of the arterial occlusion and possible therapies to prevent further insults. In most patients, a cranial computerized tomography scan and a carotid Doppler study are necessary to rule out an intracranial hemorrhage or define the extent of carotid stenosis ^141-143 . In some patients, more detailed investigations may be necessary to look for uncommon etiologies for the stroke.

Another key factor in obtaining a successful outcome is the provision of therapy to limit damage to the brain tissue. At the present time most patients who suffer an acute stroke present late to the hospital, with less than 5% of individuals appearing within 6 hours of the insult. This has presented a major challenge to the use of thrombolytic or neuroprotective agents in the treatment of an acute ischemic stroke ¹³⁶ . Every effort should be made to educate both individuals at risk and their family members to bring patients with acute stroke symptoms to an acute care facility as soon as possible after the onset of symptoms. Early arrival to a hospital with an acute stroke care unit may considerably improve prognosis.

The recognition and prompt management of complications following stroke is important. For several hours after the onset of symptoms, patients with an acute stroke are medically unstable. Several important measures, which could potentially prevent complications, can be applied to the patient with acute stroke. Most patients have an acute transient increase in their blood pressure. Unless the blood pressure is very high (more than 240/130 mm Hg) or if thrombolytic therapy is being offered to the patient, it is wise not to decrease the blood pressure acutely after the insult. Patients with a large hemispheric stroke or a brainstem stroke are at an increased risk for aspiration pneumonia; therefore, oral feeding should be withheld until a swallowing assessment has been completed. The presence of fever and hyperglycemia may also adversely affect prognosis and may require prompt attention ^143-145.

A major advance in the management of acute stroke which has generated excitement has been the introduction of therapies that may decrease the size of the ischemic infarction and improve outcome. Such therapies fall into two broad categories; thrombolytic and neuroprotective drugs. While there is considerable experimental evidence that they may have additive potential when used in combination, to date the two classes of medication have not been tested together in stroke patients.

Several different types of thrombolytic agents are used to dissolve blood clots that have led to the stroke. The three drugs used extensively in stroke research include tissue plasminogen activator (tPA), streptokinase, and urokinase ¹⁴⁶ . A major problem with the use of thrombolytic therapy after an acute stroke is the risk of intracerebral hemorrhage. This risk increases if therapy is delayed. Evidence for protection with tPA has led to its approval by the Food and Drug Administration in the United States provided the drug is administered within three (3) hours of the onset of symptoms by a team competent in the management of stroke and having 24-hour access to computerized tomography and neurosurgical services. The risk of intracerebral hemorrhage is the major limitation for general use. Intra-arterial urokinase may have fewer side effects and is currently undergoing clinical trials in acute stroke. A recent report suggests that low molecular weight heparin may also improve functional outcome if given within 24-48 hours of the onset of symptoms and continued for the first few days.

With better understanding of the mechanisms involved, it has become possible to develop medications that limit or attenuate the extent of neuronal damage. There are several types of neuroprotective drugs, which when given prior to the insult, may either prevent or significantly limit the size of the infarction. A number of such neuroprotective agents are currently undergoing clinical trials in acute stroke and subarachnoid hemorrhage ^136-138 . An advantage to the use of such medications in acute stroke is that a cranial computerized tomography scan is not necessary prior to administration of the initial dose of the drug. As well, the neuroprotective agent may potentially be offered in the ambulance, thus saving valuable time. For these agents to be clinically relevant, the drug should show protection when given after the insult, have few side effects, and be easy to administer. While no neuroprotective therapy has been shown to provide significant protection, we hope to see promising results in the next few years.

Primary Prevention

The primary prevention of stroke is achieved through risk factor modification, by either lifestyle changes or by medical intervention. Secondary prevention alters a disease process after it has become clinicaly apparent. However, in the context of vascular disease, the distinction between primary and secondary prevention becomes somewhat blurred. Secondary prevention is targeted at patients whereas primary prevention is aimed at populations. Secondary prevention generally involves treating patients who are at high risk of serious vascular events. Primary prevention largely falls in the domain of policy makers and governmental public health departments, and is concerned with interventions such as the restriction of tobacco advertising. The two approaches are complementary. While individuals at high risk may benefit greatly from a given intervention, only a small proportion of all serious vascular events occur in people at the highest risk. Most events occur among those at moderate risk. The paradox clearly mandates a multifaceted approach ¹⁴⁷ . Furthermore, because of the overlap between coronary artery disease, peripheral vascular disease, and cerebral vascular disease, stroke prevention should not be seen in isolation but as part of a bigger strategy to prevent all forms of vascular disease.

Secondary Prevention

For the purposes of this discussion, comments will be confined to the prevention of stroke after a transient ischemic attack (TIA) or after a first stroke.

Risk Factor Modification

1. Hypertension

Antihypertensive drug treatment reduces the risk of first stroke by about 40% ¹⁴⁸ . The efficacy of therapy for secondary prevention is less clear as only two small trials have been conducted among stroke survivors, and none have involved only TIA patients. The place of antihypertensive treatment in the setting of acute stroke remains unclear ¹⁴⁹ . Most physicians would probably treat hypertensive TIA patients and stroke survivors as they would patients who had not yet suffered a serious vascular event ¹⁵⁰ . For stroke patients, decisions about long-term antihypertensive treatment are best deferred for a few days after the stroke since blood pressure usually falls spontaneously during this time.

2. Hyperlipidemia

The role of hyperlipidemia in the pathogenesis of stroke, and the place of lipid lowering drugs in the prevention of stroke remain uncertain. The picture is clearer for coronary heart disease, and because TIA patients and survivors of ischemic stroke are at high risk of coronary events it seems reasonable to lower elevated plasma cholesterol levels in these individuals. The results of one trial (The Scandinavian Simvastatin Survival Study)¹⁵¹ suggest that any patient with a history of ischemic stroke or TIA, and a previous myocardial infarction, and a cholesterol level greater than 5.2 mmol/L is likely to benefit from cholesterol reduction with a statin drug. Further randomized trials are required to define more clearly who should be treated and how.

3 Smoking

Smoking is a risk factor for cerebral infarction and for subarachnoid hemorrhage ¹⁵² . It is well known that all tobacco users should be advised to quit. Several randomized trials have demonstrated the effectiveness of nicotine replacement therapy ¹⁵³ . Long-term abstinence, however, can be difficult to achieve, and requires a combination of behavioural and pharmacological approaches.

4. Alcohol

Observational studies have shown a J-shaped relationship between alcohol intake and stroke. Occasional to light alcohol consumption is protective, whereas heavy alcohol use (5 or more drinks per day) is an independent risk factor for ischemic stroke ¹⁵⁴ . How alcohol protects against stroke is unknown. Heavy alcohol intake aggravates hypertension, and may induce emboligenic cardiac problems such as atrial fibrillation and congestive cardiomyopathy. Alcohol may also have prothrombotic effects on platelet function and hemostatic mechanisms. Clinical trials of the influence of alcohol on stroke are not feasible, but prudence would seem to dictate that controlled alcohol intake is an important component of secondary stroke prevention.

5. Diet

The links between diet and stroke remain obscure. Nutrition counseling for patients who have had a stroke or TIA usually focuses on optimizing blood glucose control (in diabetic subjects), and on reducing saturated fat intake and increasing the intake of vegetables, fruit, and dietary fibre.

6. Exercise

Lack of physical exercise is associated with an increased risk of stroke ¹⁵⁵ . It is not known whether a program of increased physical activity after a stroke or TIA protects against recurrent vascular events, but there is evidence that exercise reduces mortality after myocardial infarction. Patients who have had a stroke or TIA are usually encouraged to return to normal activities and take regular moderate exercise to promote self-confidence and independence, and to help with weight control.

Antithrombotic Treatment

1. Antiplatelet Therapy

Antiplatelet treatment started a few weeks after an ischemic stroke or TIA and continued for several years reduces the risk of recurrent serious vascular events by about 25%¹⁵⁶ . Two recent large randomized controlled trials (The International Stroke Trial ¹⁵⁷ , and the Chinese Aspirin Stroke Trial ¹⁵⁸ ) have shown that additional benefit can be obtained by starting aspirin immediately after an acute ischemic stroke. Most of the data from randomized trials of antiplatelet therapy concern aspirin; yet there remains uncertainty about the most efficacious dose. Depending on their point of view, physicians may prescribe doses ranging from 80mg on alternate days to 1,300 mg daily. Other antiplatelet agents - dipyridamole, ticlopidine, and clopidogrel - although clearly effective, are not unequivocally superior to aspirin ^156,159,160 . These drugs may, however, be used in patients who cannot tolerate aspirin, or in those who experience ischemic vascular events while taking aspirin.

2. Anticoagulant Therapy

Although anticoagulants were first used to treat cerebrovascular disease more than 50 years ago, randomized controlled trials have only recently provided data to guide practising clinicians ^161-163 . Warfarin, at a dose sufficient to produce an International Normalized Ratio in the range 2.0 - 3.0, is the treatment of choice for the prevention of stroke in patients under age 75 who have atrial fibrillation and a history of hypertension, diabetes, congestive heart failure, or a thromboembolic event (including a TIA or nondisabling ischemic stroke). In such patients, a relative risk reduction of two-thirds or more is afforded by carefully controlled anticoagulant therapy. Atrial fibrillation occurring in young patients in the absence of the above mentioned risk factors is less ominous and does not require anticoagulant treatment. Among patients over age 75, the benefits of warfarin are less clear because of an increased risk of bleeding complications. In this group of patients, many physicians would opt to use aspirin instead of warfarin. In one trial involving patients with prosthetic heart valves, the combination of aspirin and warfarin was superior to warfarin alone for the prevention of stroke ¹⁶⁴ . Except in patients with atrial fibrillation or prosthetic heart valves, warfarin does not have a clearly established (evidence-based) role in secondary stroke prevention.

3. Carotid Endarterectomy

In patients who experience a carotid territory TIA or nondisabling stroke and have angiographic evidence of severe (70% or more) ipsilateral carotid stenosis, successful carotid endarterectomy performed within 6 months of the attack almost completely abolishes the risk of ischemic stroke in the territory of the operated artery over the subsequent few years ^165-166 . Because surgery is so superior to medical treatment (i.e. antiplatelet therapy and risk factor modification), establishing - at the earliest opportunity - the presence (or absence) of severe carotid stenosis is the imperative of contemporary management of the patient who presents with a carotid territory TIA or minor ischemic stroke. The role of carotid endarterectomy in the management of asymptomatic carotid stenosis is much less clear. In the Asymptomatic Carotid Atherosclerosis Study ¹⁶⁷ the absolute benefit afforded by surgery was small, such that about 170 patients had to be operated on in order to prevent one disabling stroke. It has been argued that this is not cost-effective medicine, particularly since the risk of a serious cardiac event is considerably higher than the risk of stroke. In Canada, there is consensus against endarterectomy for asymptomatic carotid stenosis ¹⁶⁸.

Tertiary Prevention

Prevention does not stop once someone has had a stroke. There is much to be done to prevent the distressing sequelae of stroke. Early mobilization reduces respiratory difficulties, thrombosis in leg veins, skin break down, contractures, incontinence, urinary tract infections, and depression. Rehabilitation increases independence, the ability of the person to return home and take up pre-stroke activities, and the ability of the family to be able to provide care. Continued participation in physical, recreational, educational, and social activities will contribute to improvement in health and quality of life. There are increasing numbers of persons in the community who are living with the sequelae of stroke and who are at risk for diminished activity level, social isolation and recurrent stroke. Services targeted at tertiary prevention are, therefore, essential if the outcome of stroke is to improve. Currently, in Canada, access to these services are minimal and threatened as provinces look for ways of cutting costs.

Increased awareness of risk factors and lifestyle changes to reduce these risk factors even after stroke will go a long way towards preventing a recurrence. The perception that "you can't teach an old dog new tricks (especially one with a stroke)" needs to be dispelled. Prevention of stroke at all levels can improve the health of Canadians.

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