Abstract
The goals of drug therapy in adult patients with heterozygous familial hypercholesterolemia (FH) are directed at reducing plasma concentrations of low density lipoproteins (LDL), with a secondary goal in selected patients to concurrently decrease elevated plasma concentrations of lipoprotein(a), triglycerides, and potentially exert favorable effects on the concentrations of high density lipoproteins (HDL). Desirable goals of therapy are to reduce concentrations of LDL cholesterol to < 130–160 mg/dL in patients without evidence of coronary artery disease, and, in my opinion, to < 100 mg/dL in patients with evidence of coronary artery disease. The bile add sequestrants, cholestyramine and colestipol, reduce LDL concentrations by 23–36%, when given in doses of 4–6 scoops/day, but reduce LDL concentrations to desirable levels in only 10–15% of patients. Similarly, nicotinic acid, in doses of 3–6 g/day, is capable of reducing LDL concentrations by up to 30%, but the majority of patients still remain hypercholesterolemic. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, which include lovastatin, simvastatin, and pravastatin, are the most effective of the currently available drugs and show dose-dependent effects on the concentrations of LDL cholesterol, which decrease by 20–45% in response to these drugs when used over the full dosage range. However, even with these agents, concentrations of LDL cholesterol remain >200 mg/dL in one-third of mate and female patients with heterozygous FH and remain >160 mg/dL in 75–80% of treated patients. Probucol and the fibrates are less effective than the first choice agents discussed above, and these drugs reduce LDL cholesterol concentrations by < 15% in patients with heterozygous FH. Optimal control of LDL concentrations in patients with heterozygous FH necessitates the use of combination drug therapy in most patients. The goals of LDL reduction necessary for primary prevention of premature coronary artery disease are achievable in the majority of patients with heterozygous FH, whereas optimal values for secondary intervention are infrequently attained.
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