Preventing recurrent ischemic stroke: A 3-step plan
To prevent recurrent stroke, address the patient’s risk factors, clear stenosis, and thin the blood
In the Losartan Intervention for Endpoint Reduction (LIFE) trial, addressing primary prevention, 9193 hypertensive patients were randomized to receive losartan or atenolol and were followed for a mean of 4.8 years.12 In the losartan arm, there was a 13% reduction in the combined endpoint of stroke, myocardial infarction (MI), and vascular death, with a 25% reduction in the rate of stroke despite a similar reduction in blood pressure in each arm.
In the largest of the trials, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), 33,357 patients with hypertension and at least 1 other vascular risk factor were randomly assigned to receive chlorthalidone, amlodipine, or lisinopril, and were followed for 4.9 years.15 No differences between treatments were found for the primary outcome (fatal coronary heart disease or nonfatal MI). In a head-to-head comparison of chlorthalidone and lisinopril, chlorthalidone yielded a 15% reduction in the rate of stroke.
Stroke is the leading cause of adult disability, the second leading cause of dementia, and the third leading cause of death in the United States. Stroke survivors are at significantly increased risk for subsequent stroke,13 with more than 75% of secondary vascular events being stroke.3 Therefore, prevention of secondary stroke saves lives, prevents disability, and is a prudent allocation of medical resources. Direct costs attributable to stroke in the United States are estimated at $28.3 billion a year, with total costs greater than $50 billion.3,14
Applying the evidence. Although no class of antihypertensive therapy is clearly superior to others for primary or secondary stroke prevention, it is clear that lowering blood pressure is effective.
Since most hypertensive stroke patients will require at least 2 agents to control blood pressure, using a thiazide diuretic or an agent to inhibit the renin-angiotensin system or both appears to be reasonable.
Once a stroke patient has stabilized, if there is no contraindication, consider starting an antihypertensive agent regardless of the baseline blood pressure.16
Hypercholesterolemia
In general, higher levels of low-density lipoprotein (LDL) cholesterol increase the risk of vascular disease. Multiple high-quality prospective randomized trials have demonstrated improved vascular outcomes for patients with coronary artery disease.17 However, the direct link to secondary prevention after stroke is somewhat tenuous.18
Clinical trials with statin therapy. Several trials have reported a benefit with statin therapy for primary stroke prevention. The Scandinavian Simvastatin Survival Study (4S) was the first to demonstrate that lowering cholesterol with a statin drug can reduce the risk of stroke by 30% compared with placebo in patients with hypercholesterolemia at high risk for vascular disease.19
The Cholesterol And Recurrent Events (CARE) trial confirmed the benefit of statin therapy in reducing the rate of stroke in a population at high vascular risk.20 In the CARE trial, pravastatin reduced the rate of stroke by 31% compared with placebo.
The Medical Research Council Heart Protection Study (HPS) randomized 20,536 high-risk patients to receive 40 mg simvastatin daily or placebo.21 Researchers found a statistically significant 25% risk reduction in prespecified endpoint stroke with an even more impressive reduction of 30% in ischemic stroke. However, in the non-prespecified analysis of patients entering the trial with ischemic stroke or TIA, no benefit of statin therapy was found for secondary stroke prevention.22
Applying available recommendations. Trials are under way to prospectively test the benefit of statin therapy for secondary stroke prevention.23 Until the results of those trials are available, guidelines are available to help with decision making. The NCEP III guidelines recommend a target LDL cholesterol level below 100 mg/dL for patients with symptomatic atherosclerotic disease.24
Cardiac risk factors
Atrial fibrillation (AF), valvular disease, coronary artery disease, and recent large MI increase the risk for stroke. Of these, AF shows the strongest association. AF increases with age and is found in 5.9% of patients older than 65 years.4 It is present in more than one third of stroke patients older than 75 and is the most common cause of ischemic stroke in this age group.25,26 Although much less common than nonvalvular AF, valvular AF poses an even greater risk.7
Applying the evidence. Prescribe war-farin for stroke patients with AF (see Anticoagulation, below). While there is a paucity of data on prevention in other causes of cardioembolic stroke, most patients with cardioembolic stroke may benefit from chronic anticoagulation.
