Colestipol is used as an adjunct to dietary therapy to decrease elevated serum total and low-density lipoprotein (LDL)-cholesterol concentrations in the treatment of primary hypercholesterolemia (type IIa hyperlipoproteinemia). Although the drug may also lower plasma cholesterol concentrations in patients with other types of dyslipidemia, it may increase plasma triglyceride concentrations and, therefore, should be used with caution in patients with baseline triglyceride concentrations of 250-299 mg/dL. The drug should not be used alone in patients with baseline fasting triglyceride concentrations of 300 mg/dL or greater or in those with primary dysbetalipoproteinemia (Fredrickson type III).
The American College of Cardiology (ACC)/American Heart Association (AHA) guideline for management of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults states that nondrug therapies (i.e., lifestyle modifications), which include adherence to a heart-healthy diet, regular exercise, avoidance of tobacco products, and maintenance of a healthy weight, are the foundation of atherosclerotic cardiovascular disease (ASCVD) prevention. Drug therapy is not a substitute for but an adjunct to these nondrug therapies and measures, which should be continued when drug therapy is initiated. Because drug therapy is likely to continue for many years or a lifetime, the patient should be fully apprised of the goals and potential adverse effects of drug therapy. For additional details on lifestyle modifications, consult the most recent AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk (available at http://www.cardiosource.org or http://my.americanheart.org).
The ACC/AHA cholesterol management guideline states that nonstatin therapies (e.g., bile acid sequestrants) do not provide acceptable ASCVD risk reduction benefits compared to their potential for adverse effects in the routine prevention of ASCVD. The guideline states that nonstatin drugs may be useful as adjuncts to statin therapy in high-risk patients (e.g., patients with ASCVD, patients with LDL-cholesterol concentrations of 190 mg/dL or higher, patients with diabetes mellitus) who have a less-than-anticipated response to statins, are unable to tolerate even a less-than-recommended intensity of a statin, or are completely intolerant to statin therapy. When a nonstatin drug is required, selection of the nonstatin drug should be based on a favorable benefit-risk ratio (i.e., demonstrated benefit of ASCVD risk reduction outweighs risks of adverse effects and drug interactions) and patient preferences. For additional details on prevention of ASCVD, and also consult the most recent ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults (available at http://www.cardiosource.org or http://my.americanheart.org).
Dietary management often is relatively effective in young children (2-5 years of age) with heterozygous familial hypercholesterolemia; however, older children with this disorder usually require the addition of drug therapy. Bile acid sequestrants (e.g., colestipol) or statins generally are considered the initial drugs of choice for the management of dyslipidemia or primary prevention of coronary heart disease (CHD) in selected children and adolescents (i.e., those 10 years of age and older with higher risk of developing CHD) in whom initial nonpharmacologic therapy (i.e., a 6- to 12-month trial of therapeutic lifestyle changes) does not provide adequate response. A bile acid sequestrant combined with a statin may be useful in hypercholesterolemic patients in whom initial drug therapy does not provide an adequate response or is not tolerated. Children with homozygous familial hypercholesterolemia usually respond poorly to combined dietary management and drug (e.g., combined bile acid sequestrant and niacin) therapy. More radical forms of therapy (e.g., plasma exchange, portacaval shunt, liver transplantation) combined with adjuvant drug therapy (e.g., bile acid sequestrants and niacin) and dietary management may be necessary in homozygous patients, but specialists should be consulted.
Colestipol, in conjunction with dietary therapy, has been shown to be more effective than diet alone or placebo in the treatment of hypercholesterolemia. However, in some patients, serum cholesterol concentrations may return to or exceed baseline concentrations during colestipol therapy. Colestipol and cholestyramine are equally effective in lowering plasma cholesterol concentrations. The choice of bile acid sequestrant generally is individualized based on patient tolerance, including palatability and taste preference, and cost. Patients with heterozygous familial type II hyperlipoproteinemia (familial hypercholesterolemia) who do not respond adequately to colestipol therapy and dietary management may benefit from the addition of niacin to the therapeutic regimen. Combined colestipol and niacin therapy in these patients has been reported to further reduce serum total cholesterol and LDL-cholesterol, to increase serum high-density lipoprotein (HDL)-cholesterol, and to decrease serum triglyceride concentrations. This combination has also reduced xanthomas and the progression of coronary arterial lesions in these patients. There is some evidence that combined therapy with colestipol, niacin, and lovastatin (an HMG-CoA reductase inhibitor) provides complementary effects in reducing LDL-cholesterol, since reductions were greater with triple-drug therapy than with various two-drug combinations in a limited number of patients with severe familial (heterozygous or homozygous) hypercholesterolemia; additional study is necessary.
In the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT), long-term administration of cholestyramine resin to men with type II hyperlipoproteinemia who received dietary management was shown to reduce the risk of CHD. There was a 19% reduction in the combined incidence of CHD death and nonfatal myocardial infarction in this study. It is likely that similar effects would be produced by other bile acid sequestrants, such as colestipol, that have similar effects on serum cholesterol concentrations through the same general mechanism.
For further information on the role of antilipemic therapy in the treatment of lipoprotein disorders, the prevention of cardiovascular events, and other conditions, see General Principles of Antilipemic Therapy in the HMG-CoA Reductase Inhibitors General Statement 24:06.08.