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How effective is drug therapy in heterozygous familial hypercholesterolemia?
1Department of Medicine, Oregon Health Sciences University, Portland 97201-3098.
Insights
Drug therapy for familial hypercholesterolemia (FH) aims to lower LDL cholesterol. While HMG CoA reductase inhibitors are most effective, many patients still have elevated LDL cholesterol levels.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
Background:
- Familial hypercholesterolemia (FH) is a genetic disorder characterized by high LDL cholesterol levels.
- Effective management of FH is crucial to prevent cardiovascular disease.
Purpose of the Study:
- To review the goals of drug therapy for adult patients with heterozygous FH.
- To evaluate the efficacy of different drug classes in reducing LDL cholesterol concentrations.
Main Methods:
- Review of current therapeutic strategies for FH.
- Analysis of the effectiveness of bile acid sequestrants, nicotinic acid, and HMG CoA reductase inhibitors.
Main Results:
- Bile acid sequestrants (cholestyramine, colestipol) reduce LDL by 23-36% but achieve target levels in only 10-15% of patients.
- Nicotinic acid (3-6 g/day) reduces LDL by up to 30%, but most patients remain hypercholesterolemic.
- HMG CoA reductase inhibitors (lovastatin, simvastatin, pravastatin) are most effective, reducing LDL by 20-45%, yet one-third of patients still exceed target levels.
Conclusions:
- HMG CoA reductase inhibitors represent the most effective current pharmacotherapy for FH.
- Despite available treatments, achieving optimal LDL cholesterol targets remains a challenge for many FH patients.
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 acid 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 male and female patients with heterozygous FH and remain > 160 mg/dL in 75-80% of treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)