Guidelines for vascular risk factor reduction for secondary prevention of ischemic stroke

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By Douglas J Lanska MD MS MSPH

Article under review:

Furie KL, Kasner SE, Adams RJ, et al; on behalf of the American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Clinical Cardiology, and Interdisciplinary Council on Quality of Care and Outcomes Research. Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack. A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2010 Oct 21. [Epub ahead of print]
http://stroke.ahajournals.org/cgi/reprint/STR.0b013e3181f7d043v1

Purpose:

The purpose of this guideline is to provide up-to-date recommendations for prevention of stroke among individuals who have survived a previous stroke or transient ischemic attack (TIA). Note: This Journal Club will summarize the portions of the guidelines concerning vascular risk factor control for all patients with TIA or ischemic stroke (Section I, pp. 2-10).

Methods:

Systematic literature synthesis and interpretation by expert panel. Literature searches were limited to peer-reviewed English-language sources concerning human subjects, generally appearing in journals listed in Index Medicus and published as of August 1, 2009. Recommendations follow the American Heart Association classifications of level of certainty of treatment effect, based on the quality, number, and consistency of the supporting evidence. Details of the guideline development process of the Stroke Council of the American Stroke Association are given in a separate document, the Stroke Council Guideline Development Manual.

Results/summary:

The following are the article's recommendations for controlling the risk factors for prevention of stroke among individuals who have survived a previous stroke or TIA:

Hypertension: Normal blood pressure has been defined by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) as < 120/80 mm Hg. Elevations of both systolic and diastolic blood pressure are associated with an increased risk of stroke, without a clear threshold evident.

Because data are lacking to guide the immediate management of elevated blood pressure in the setting of acute stroke, caution is advised particularly within the first 24 hours. Blood pressure reduction is recommended for prevention of stroke progression and other vascular events (eg, myocardial infarction) for patients more than 24 hours after a TIA or ischemic stroke.

Treatment with antihypertensive medications has been associated with significant reductions in the occurrence of subsequent stroke, myocardial infarction, and all vascular events combined. Note that the benefit of blood pressure reduction extends to patients without a documented history of hypertension. Although the optimal target blood pressure and degree of reduction are uncertain, benefit has been shown for average reductions of 10/5 mm Hg. Blood pressure lowering has been associated with a 30% to 40% reduction in stroke risk in meta-analyses of randomized controlled trials, with the degree of risk reduction correlated with the magnitude of the reduction in blood pressure. The optimal drug regimen is uncertain, as data comparing different agents are lacking; however, diuretics alone or in combination with an angiotensin-converting enzyme inhibitor are useful.

Lifestyle modifications are associated with reduction in blood pressure and are considered a "reasonable part of a comprehensive antihypertensive therapy." These modifications include the following: salt restriction; weight loss; consumption of a diet rich in fruits, vegetables, and low-fat dairy products; regular aerobic physical exercise; and limited alcohol consumption.

Diabetes: Normal fasting glucose is defined as < 100 mg/dL, whereas impaired fasting glucose is defined as from 100 to 125 mg/dL. A fasting glucose of > 125 mg/dL, a "casual" or "random" glucose of > 200 mg/dL, or a hemoglobin A1c of at least 6.5% in association with symptoms attributable to hyperglycemia meet current threshold criteria for diabetes. Although "normal" hemoglobin A1c values are considered to be 6.0% or lower, inadequate control of diabetes is defined as a hemoglobin A1c level of > 7%.

Diabetes is clearly associated with first stroke and is likely an independent predictor of recurrent stroke. The prevalence of diabetes among those with ischemic stroke is 15% to 33%, some 2 to 4 times the prevalence in the general adult population of the United States.

Several major randomized trials of intensive glucose management in diabetic patients with a history of cardiovascular disease, stroke, or other vascular risk have all failed to demonstrate a reduction in cardiovascular events or death associated with intensive glucose management. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was halted prematurely because of an increased risk of death in patients randomized to the active treatment arm. Because of these collective results, the glycemic control target for diabetics following stroke or TIA remains an HgbA1c of < 7.0% (rather than previously proposed targets, eg, < 6.5%).

Lipids: Epidemiologic studies have demonstrated modest associations of fasting lipid values and ischemic stroke risk, particularly for elevated total cholesterol or low-density lipoprotein cholesterol (LDL-C), but more recently for elevated triglycerides or low high-density lipoprotein cholesterol (HDL-C). (Note: Epidemiologic studies have also suggested an inverse association between LDL-C and risk of intracerebral hemorrhage.)

In patients with coronary heart disease, LDL-C lowering reduces total mortality, coronary mortality, major coronary events, and stroke. Patients with atherosclerotic ischemic stroke or TIA, with an elevated total cholesterol or comorbid coronary heart disease, should be managed according to existing guidelines of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III.

Primarily because of the results of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial, it is now clear that reducing LDL-C is also very beneficial for patients with stroke or TIA who are without known coronary heart disease or elevations in total cholesterol. In the SPARCL trial, patients with stroke or TIA, LDL-C levels between 100 and 190 mg/dL, and no known history of coronary heart disease were randomly assigned to an active treatment arm of 80 mg of atorvastatin daily or placebo. During a median follow-up of 5 years, there was an absolute reduction in risk of (fatal or nonfatal) stroke of at least 2.2% and reduction in risk of major cardiovascular events of at least 3.5% (because of cross-overs and high rates of discontinuation of assigned therapy, the results are thought to underestimate the magnitude of the true treatment effect in fully compliant patients). Statin therapy was generally well tolerated with no cases of liver failure and no excess in cases of myopathy, myalgia, or rhabdomyolysis. Achieving an LDL-C level of < 70mg/dl was associated with a 28% reduction in risk of stroke (without an increase in risk of hemorrhagic stroke), and patients with at least a 50% reduction in LCL-C had a 35% reduction in risk of stroke (again without an increase in risk of hemorrhagic stroke).

Therefore, in patients with atherosclerotic ischemic stroke or TIA who are without known coronary heart disease and who have an LDL-C level of at least 100 mg/dL, statin therapy with intensive lipid-lowering effects is recommended to reduce the risks of both stroke and cardiovascular events. To achieve maximum benefit among patients with atherosclerotic ischemic stroke or TIA who are without known coronary heart disease, it is considered "reasonable" to set targets of LDL-C of < 70 mg/dL or at least a 50% reduction in LDL-C.

Non-statin agents for treating dyslipidemia can be used by stroke and TIA patients who cannot tolerate statins, but data supporting their efficacy for secondary stroke prevention are sparse. The current guideline indicates that niacin or gemfibrozil "may be considered" for patients with ischemic stroke or TIA.

Cigarette smoking: Cigarette smoking is a major independent risk factor for ischemic stroke (as well as for myocardial infarction and peripheral vascular disease). Growing evidence indicates that passive smoke exposure also increases the risk of cardiovascular disease, including stroke. Available data pertain to primary prevention but are also considered applicable to secondary prevention of ischemic stroke or TIA. Healthcare providers should strongly advise every patient with stroke or TIA who has smoked in the last year to quit smoking. Effective approaches to helping smokers quit include physician counseling, nicotine replacement products, and oral smoking cessation medications.

Alcohol consumption: Alcoholism and heavy drinking are risk factors for all stroke subtypes. Most studies have indicated a J-shaped association between alcohol consumption and risk of incident ischemic stroke, with a suggested protective effect with light consumption and an elevated risk with heavy consumption (or with binge drinking). Most available data on alcohol consumption and stroke risk concern primary prevention. Although no studies have demonstrated that reduction of alcohol intake decreases risk of recurrent stroke, it is nevertheless recommended that patients with ischemic stroke or TIA who are heavy drinkers should be strongly counseled to eliminate or reduce their intake of alcohol. Intake of no more than 2 drinks per day for men and 1 drink per day for non-pregnant women "may be reasonable." Regardless of the reported J-shaped association of alcohol consumption and stroke risk, the current guideline advises that nondrinkers should not be counseled to start drinking.

Obesity: Although obesity is an established independent risk factor for coronary heart disease and premature mortality, no study has demonstrated that weight reduction reduces risk of stroke recurrence. The current guidelines make no recommendations on this issue.

Physical activity: Physical activity can positively impact several vascular risk factors. Unfortunately, post-stroke neurologic deficits and disability often predispose patients to activity intolerance and physical deconditioning. Nevertheless, resumption of physical activity and exercise after a stroke can help optimize physical performance, functional capacity, and quality of life. For patients with ischemic stroke or TIA who are capable of participating in physical activity, the current guideline recommends at least 30 min of moderate-intensity physical activity 1 to 3 times per week, sufficient to break a sweat or noticeably raise the heart rate. Suggested activities include brisk walking or riding an exercise bicycle.

Metabolic syndrome: There is insufficient evidence to support screening patients for the metabolic syndrome after a stroke or TIA. For patients who are nevertheless identified as having the metabolic syndrome, management should include lifestyle modification counseling concerning diet, exercise, and weight loss for vascular risk factor reduction. Preventive care for patients with the metabolic syndrome should include appropriate treatment for each of the individual syndrome components that are also recognized stroke risk factors, particularly hypertension and dyslipidemia.