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Medical Treatment to Prevent Transient Ischemic Attacks and Ischemic Stroke


The distinction between a transient ischemic attack (TIA) and stroke is made by duration of symptoms: The duration of a TIA is less than 24 hours. A TIA is a harbinger of stroke in up to 17% of patients, most often during the first week after the event. Ischemic stroke accounts for 88% of all strokes. Classic subtypes of stroke have been well defined ( Box 1 ). More than 75% of strokes are first events, allowing an opportunity for meaningful intervention.

BOX 1
Types of Ischemic Stroke

  • Large artery atherosclerotic infarction: extracranial or intracranial

  • Embolism from cardiac source

  • Small vessel disease

  • Causes other than atherosclerosis or embolism such as dissection, hypercoagulable states, or sickle cell anemia

  • Infarcts of undetermined cause

Modification of Risk Factors

The risk for stroke and TIA is affected by various modifiable and nonmodifiable risk factors ( Box 2 ). Treatment recommendations have been established ( Table 1 ).

BOX 2
Risk Factors Associated with Adult Ischemic Stroke

Nonmodifiable Risk Factors

  • Sex

  • Age

  • Low birth weight

  • Family history of stroke or transient ischemic attack

  • Specific genetic predisposition

    • Risk factor tendency (diabetes, hyperlipidemia, etc.)

    • Homocysteinemia

    • Variants in chromosome 9p21 and 4q25

    • Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CARDASIL)

    • Fabry disease

    • Sickle cell anemia ∗

      ∗ Treatment with proven reduction of stroke exists.

Modifiable Risk Factors

  • Hypertension

  • Diabetes mellitus

  • High total cholesterol

  • Low HDL cholesterol

  • Atrial fibrillation

  • Carotid artery stenosis

  • Hormone treatment

    • Postmenopausal hormone replacement

    • Oral contraceptive use

  • Nutritional factors

    • Elevated sodium intake

    • Low potassium intake

  • Physical inactivity

  • Obesity

  • Cigarette smoking

Potentially Modifiable Risk Factors with Less Evidence

  • Hyperhomocysteinemia

  • Excessive alcohol consumption

  • Drug abuse (heroin and cocaine)

  • High Lp(a)

  • Anti-phospholipid antibodies

  • Periodontal disease

Other

  • Presence of other diseased arterial beds: coronary and peripheral artery disease

  • Evidence for various infections such as Chlamydia pneumonia, Helicobacter pylori

  • Elevated CRP

CRP , C-reactive protein; HDL , high-density lipoprotein; Lp(a) , lipoprotein (a).

TABLE 1
Medical Risk Factor Modification for Primary Stroke Prevention
Risk Factor Recommendation Comment
Hypertension BP <140/90 mm Hg BP lowering is more important than choice of medication; diabetic patients may benefit from further BP reduction
Diabetes mellitus Multifactor risk factor modification may be better than focusing on targeting glucose alone Hb A1c <7% has not been shown to reduce risk of stroke
Hyperlipidemia Patients with elevated cholesterol, atherosclerosis anywhere: LDL <100 mg/dL
Diabetics: LDL <70 mg/dL		 First line: statins
Second line: bile-acid sequestrants and niacin
Tobacco abuse Combined pharmacologic and behavioral smoking-cessation therapy Lack of direct evidence
BP , Blood pressure; Hb A1c , hemoglobin A1c; LDL , low-density lipoprotein cholesterol.

Hypertension

Hypertension is related to stroke in a graded, continuous manner, and stroke risk is increased even when blood pressure levels are considered normal by current guidelines. Patients with prehypertension should be encouraged to control their pressure with nonpharmacologic lifestyle measures. The Joint National Committee (JNC) 7 guidelines for the classification and treatment of hypertension have been published ( Table 2 ).

TABLE 2
Classification and Treatment of Blood Pressure
From Goldstein LB, Bushnell CD, Adams RJ, et al: Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association, Stroke 42:517–584, 2011. Used with permission. ©2011 American Heart Association, Inc.
Classification Systolic Blood Pressure (mm Hg) Diastolic Blood Pressure (mm Hg) No Compelling Indication ∗ With Compelling Indication ∗
Normal <120 <80 No antihypertensive drug No antihypertensive drug
Prehypertension 120–139 80–89 No antihypertensive drug Drugs for compelling indication
Stage I hypertension 140–159 90–99 Thiazide-type diuretic for most; may consider ACEI, ARB, CCB, BB, or combination Drugs for compelling indication, other drugs as needed
Stage II hypertension ≥160 ≥100 Two-drug combination for most, usually a thiazide diuretic and a choice of ACEI, ARB, CCB, or BB Drugs for compelling indication, other drugs as needed
ACEI , Angiotensin converting enzyme inhibitor; ARB , angiotensin receptor blocker; BB , β-blocker; CCB , calcium channel blocker.

∗ Lifestyle modifications are encouraged for all and include weight reduction for overweight patients, limitation of ethanol intake, increased aerobic physical activity (30–45 minutes daily), reduction of sodium intake (2.34 g), maintenance of adequate dietary potassium (120 mmol/day), smoking cessation, and DASH diet (rich in fruits, vegetables, and low-fat dairy products and reduced in saturated and total fat).

A meta-analysis of 29 trials including 162,341 patients concluded that stroke risk is effectively reduced by lowering pressure (23%; 95% confidence interval [CI], 5%–37%). Most of the effect was not a direct result of the chosen pharmacologic regimen but rather was secondary to absolute reduction of blood pressure. Calcium channel blocker–based regimens showed a trend toward better efficacy when compared with β-blocker, diuretic-based (7%; CI, 1%–14%), or angiotensin converting enzyme (ACE) inhibitor–based regimens (12%; CI, 1%–25%). Current guidelines suggest that blood pressure should be maintained below 140/90 mm Hg in asymptomatic patients with extracranial carotid or vertebral artery atherosclerosis.

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