Cholestyramine resin is used as an adjunct to dietary therapy to decrease elevated serum total and low-density lipoprotein (LDL) cholesterol concentrations in the management of primary hypercholesterolemia (type IIa hyperlipoproteinemia). Although cholestyramine may also lower plasma cholesterol concentrations in patients with other types of dyslipidemia, the drug 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 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., cholestyramine) 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 an 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.
Cholestyramine and colestipol hydrochloride are equally effective in lowering serum cholesterol concentrations. The choice of bile acid sequestrant generally is individualized based on patient tolerance, including palatability and taste preference, and cost. Cholestyramine is generally more effective in heterozygous familial hypercholesterolemia than in homozygous familial hypercholesterolemia; however, it has been reported that even among heterozygotes, response to the drug is variable. In patients with type IIb hyperlipoproteinemia, the effect of cholestyramine on very low-density lipoprotein (VLDL) and triglyceride concentrations must be carefully monitored; calorie control or adjunctive therapy may be required. In patients with primary type IIa hyperlipoproteinemia in whom a regimen of diet and cholestyramine or colestipol hydrochloride therapy has not resulted in normal serum cholesterol concentrations, niacin may be a useful addition to therapy.
In the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT; a large, multicenter, placebo-controlled study), long-term (up to 7 years) administration of cholestyramine resin to asymptomatic men with primary hypercholesterolemia (type II hyperlipoproteinemia) who received dietary management was shown to reduce the risk of CHD. Average plasma concentrations of total cholesterol and LDL were reduced by 13.4 and 20.3%, respectively, in patients in this study and were associated with a 19% reduction in the combined incidence of CHD death and nonfatal myocardial infarction; however, the difference in overall mortality was similar in the cholestyramine-treated and placebo groups. These findings indicate that reducing plasma total cholesterol concentrations by reducing plasma LDL concentrations may decrease the incidence of morbidity and mortality associated with CHD in males at high risk of developing CHD secondary to increased plasma LDL concentrations.
Additional findings of the LRC-CPPT suggest that plasma high-density lipoprotein (HDL) cholesterol concentrations are inversely related to the risk of morbidity and mortality associated with CHD in males with hypercholesterolemia. In cholestyramine-treated patients, each 1-mg/dL pretreatment increment above the overall mean pretreatment plasma HDL-cholesterol concentration (44.3 mg/dL) was associated with a 5.5% reduction in risk of death attributable to CHD or nonfatal myocardial infarction over a 7- to 10-year period, and each 1-mg/dL increase in plasma HDL-cholesterol during therapy from the patient's pretreatment level was associated with a 4.4% risk reduction during this period. Although mean HDL-cholesterol concentrations in cholestyramine-treated patients exceeded those of patients receiving placebo during each year of the trial, differences in CHD between the groups could not be explained by differences in HDL-cholesterol alone. Cholestyramine therapy appeared to reduce the risk of CHD to a greater extent in those patients who maintained the highest HDL-cholesterol concentrations, and it was suggested that relatively high HDL-cholesterol prior to and during therapy may have enhanced the beneficial effect of cholestyramine-induced reductions in plasma LDL concentrations on CHD risk.
There is also some evidence that cholestyramine therapy combined with dietary management may have a beneficial effect in modifying the rate of progression of CHD in hypercholesterolemic patients with CHD (e.g., by slowing progression and/or inducing regression of atherosclerosis in coronary arteries).
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.
Pruritus Associated with Partial Cholestasis
Cholestyramine resin is used for the relief of pruritus associated with partial cholestasis. The resin provides symptomatic relief of pruritus associated with partial obstructive jaundice including primary biliary cirrhosis and other incomplete biliary obstructions; the effect of the drug on serum cholesterol in these patients is variable. Cholestyramine resin usually has no effect on pruritus or serum bile acid concentrations in patients with relatively complete biliary obstruction, and the resin is ineffective in complete atresia in which no bile products reach the intestine. Relief of pruritus usually occurs within 1-3 weeks after initiation of therapy. Withdrawal of the drug usually results in an increase in serum concentrations of bile acids and return of pruritus within 1-2 weeks.
Cholestyramine resin has been used as an adjunct in the treatment of cardiac glycoside toxicity in a limited number of patients. When administered soon after ingestion of a cardiac glycoside, cholestyramine may reduce initial absorption of the glycoside. When administered after onset of toxicity due to digitoxin (no longer commercially available in the US), the resin also may reduce the duration of toxicity by binding digitoxin in the GI tract during enterohepatic circulation of the glycoside. However, most clinicians believe that cholestyramine is not useful when cardiac glycoside toxicity is life-threatening.
Cholestyramine has been used with some success in the management of diarrhea associated with excess fecal bile acids, pseudomembranous colitis, erythroprotoporphyria, and acquired hyperoxaluria. Cholestyramine has been used to decrease the biological half-life of chlordecone. The resin has also been used as an adjunct in the management of chlordane toxicity to enhance the fecal elimination of heptachlor.