Preventing recurrent ischemic stroke: A 3-step plan
To prevent recurrent stroke, address the patient’s risk factors, clear stenosis, and thin the blood
- Once a stroke patient has stabilized, if there is no contraindication, consider starting an antihypertensive agent regardless of the baseline blood pressure.
- For symptomatic patients with high-grade carotid stenosis (70% to 99%), plan a course of medical management plus carotid endarterectomy (CEA). With moderate carotid stenosis (50% to 69%), CEA offers only moderate stroke risk reduction.
- When aspirin is the antiplatelet drug of choice, it is reasonable to use daily doses between 50 mg and 325 mg.
For patients with atherosclerotic ischemic infarction, 3 steps are needed to achieve the goal of preventing recurrent stroke: address risk factors, clear blocked arteries, and thin the blood.
Step 1: Address risk factors
Risk factors that are non-modifiable put patients at highest risk for recurrent stroke and dictate more aggressive management measures.
Advanced age is the most serious non-modifiable risk factor for stroke.1 Risk of stroke in those older than 65 years is 16 to 25 times higher than the risk for younger people.2
Sex, family history, race, ethnicity, and geographic location also show a positive correlation with stroke incidence. Men are 1.25 times more likely to suffer stroke than women,1 although women account for 60% of stroke fatalities.3 The “stroke belt,” a cluster of 11 states in the southeastern United States, has considerably higher stroke mortality than the country as a whole.4 African Americans are at greater risk for primary ischemic stroke and stroke mortality than are whites.3
TABLE 1 lists modifiable risk factors.5 Studies show that even after a stroke, these factors are often not aggressively treated, with most patients falling outside guideline recommendations for treatment of at least 1 risk factor.6 In risk management, the greatest benefit is in controlling hypertension.
TABLE 1
Modifiable risk factors for ischemic stroke in general population
| FACTOR | PREVALENCE (%) | RELATIVE RISK |
|---|---|---|
| Hypertension | 25–40 | 3–5 |
| Elevated total cholesterol level (>240 mg/dL [6.21 mmol/L]) | 6–40 | 1.8–2.6 |
| Physical inactivity | 25–50 | 2.0–3.5 |
| Smoking | 25 | 1.5 |
| Diabetes | 4–20 | 1.8–3.0 |
| Obesity | 18 | 1.8–2.4 |
| Asymptomatic carotid stenosis (>50%) | 2–8 | 2 |
| Alcohol consumption (>5 drinks/d) | 2–5 | 1.6 |
| Atrial fibrillation | 1 | 5 (nonvalvular) 17 (valvular) |
| Modified from: Straus SE, et al. JAMA 2002; 288:1388–1395. | ||
Hypertension
Up to 50% of all strokes are attributable to hypertension,1,7 making this the most commonly encountered modifiable risk factor. Risk of stroke rises proportionately with increasing blood pressure. Systolic levels of 160 mm Hg or higher, or diastolic levels of 95 mm Hg or higher, carry a relative risk of approximately 4.1,7
Even small reductions in blood pressure decrease the risk of stroke substantially.9
The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recently released its JNC 7 Report,5 which says that increased risk for cardiovascular disease begins at systolic blood pressure of 115 mm Hg and diastolic blood pressure of 75 mg Hg.
The current recommendation for blood pressure control is <140/90 mm Hg, with tighter control (130/85 mm Hg) being prescribed for patients with diabetes.8 The JNC 7 report established a new classification: prehypertension (120/80 mm Hg to 130/89).5 For secondary stroke prevention, studies are under way to investigate the safety and efficacy of more aggressive medical management to target a systolic blood pressure target of 120 to 130 mm Hg.
Clinical trials with antihypertensive agents. Recent trials using various antihypertensive therapies have yielded apparently contradictory data. The only prospective randomized trial of antihypertensive agents focusing on secondary stroke prevention was the Perindopril Protection Against Recurrent Stroke Study (PROGRESS). It enrolled 6105 patients with a history of stroke or transient ischemic attack (TIA) within 5 years of randomization. Patients were randomized to receive placebo or perindopril with or without indapamide (added at the treating doctor’s discretion) and were followed for 4 years.9
Patients in the treatment arm had a mean blood pressure reduction of 9/4 mm Hg. Relative risk reduction for stroke in the treatment arm was 28%. Stroke rate decreased by 43% (blood pressure reduction 12/5 mm Hg) for patients prescribed perindopril plus indapamide, while monotherapy with perindopril did not significantly reduce stroke rate. Benefit was found for patients not considered hypertensive at entry; the number of non-hypertensive patients needed to treat to prevent 1 major vascular event was 22.10
The Heart Outcomes Prevention Evaluation (HOPE) trial studied both primary and secondary stroke prevention, randomizing 9297 patients age 55 or over with high risk for vascular disease (coronary artery disease, stroke, peripheral vascular disease, or diabetes plus at least 1 other cardiovascular risk factor).11 Patients were treated with ramipril or placebo and followed for 5 years. The ramipril arm had a mean blood pressure reduction of 3/2 mm Hg, and exhibited a statistically significant 31% relative risk reduction in stroke. The risk reduction appears to be out of proportion to the blood pressure reduction, suggesting additional benefit from the angiotensin-converting enzyme inhibitor independent of its antihypertensive effect.
