Drugs for Reducing Cholesterol Levels in Persons at Risk for Stroke

ABSTRACT & COMMENTARY
Source: Schectman G, Hiatt J. Dose-response characteristics of cholesterol-lowering drug therapies: Implications for treatment. Ann Intern Med 1996;125:990-1000.

This important review discusses the major, currently available drugs that may reduce abnormal serum cholesterol levels. Abnormal lipid metabolism provides a major risk factor for coronary artery disease (CAD) and, to a somewhat lesser degree, cerebral vascular disease. Many neurologists, when finding incidental hypertension among their patients, wish to treat this stroke threat themselves. The principle may especially hold when finding untreated hypercholesterolemia as an additional treatment to protect against secondary stroke. Accordingly, Neurology Alert hereby provides guidelines for dietary formulas and therapeutic anticholesterol therapy.

Most patients with serum cholesterol values below 210-220 mg/dL can be treated by diet alone. Patients with cholesterol levels higher than 250-300 mg/dL, however, have an especially high risk of heart disease or stroke. This is particularly important if accompanied by male sex, hypertension, smoking, diabetes mellitus, a weight more than 30% above normal, a family history of CAD or stroke, or low high-density lipoprotein (HDL) levels (< 35 mg/dL). To prevent a stroke provides a patient with far more neurologic health than being treated for one, no matter how mild.

If considering antilipid treatment on the basis of finding high levels on a routine blood analysis, confirmatory tests should be obtained. These would include measuring total cholesterol, HDL, low-density lipids (LDL), and triglycerides following 14 hours of fasting. Maximal normal values consist of total cholesterol below 220 mg/dL; LDL below 130 mg/dL; and HDL above 35 mg/dL. Total triglycerides above 220 suggest possible non-cholesterol diseases and should be first investigated.

Best recommendations for subsequent treatment given by the above authors follows.

Diet. Low cholesterol diets are readily available from books and from skilled dietitians who can emphasize tastiness. They are best recommended as a first step for patients with cholesterol levels between 250-350. Maximal improvement seldom exceeds ± 8% reduction of serum cholesterol or LDL. Programs including attention to other risk factors indicated above may achieve better results.

LDL Elevation. Maximal normal LDL level is 2.59 mm/L (130 mg/dL); ideal level is 100 mg/dL. Recommended treatment for persons with serum triglycerides lower than 250 mg/dL and LDL levels between 130/160 mg/dL should first be given lipid-lowering diet therapy. Those above 150-160 mg/dL should be started on a moderate dose of statin, 20 mg daily for levostatin, flurastatin, and prevastatin or 10 mg for simvastatin (see Table). Failure to reduce LDL levels within four months should lead to adding a bile acid sequestrant 10-15 mg daily, which provides synergistic responses. Bile acid sequestrants bind cholesterol in the gut, preventing absorption, but gastrointestinal symptoms may limit pleasant use to 2-3 scoops per day.

Should such a regimen (particularly the ingestion of sequestrants) become insufficient, niacin may effectively increase low HDL levels (i.e., < 35 mg/dL). Niacin brings dose-related improvements, but its use potentially risks producing a number of uncomfortable or even dangerous risks. Common complications include: flushing, itchy rash, myalgia, hyperglycemia, liver toxicity, etc. Patient one-year tolerance is less than 50%. It is probably too risky for general neurologic application, but it does increase HDL cholesterol levels, improving LDL/HDL ratios. Niacin’s usage should best be guided by physicians experienced with using the drug.

Strategies

Simple is best. Maintain drug therapy; exclude diabetes, hypothyroidism, nephrotic syndrome, obstructive liver disease, if triglycerides are above 200.

Moderate. LDL cholesterol levels above 20-25% higher than 130 mg/L; modest dose of statins (drugs that inhibit cholesterol production) best choice.

Mild. Hypercholesterolemia (triglycerides > 180-220 mg); dietary reduces ± 7% at best.

Treatment. See Table. —fp