What are bile acid sequestrants (BAS)?

From the Guidelines

Bile acid sequestrants are a reasonable addition to statin therapy in patients with high cardiovascular risk who require additional LDL-C lowering, as recommended by the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1.

Mechanism of Action and Indications

Bile acid sequestrants, including cholestyramine, colestipol, and colesevelam, work by binding to bile acids in the intestine, preventing their reabsorption and promoting their excretion in stool. This mechanism of action leads to a decrease in the bile acid pool, which in turn increases the conversion of cholesterol to bile acids in the liver, resulting in increased clearance of LDL-C from the blood and decreased serum LDL-C levels. They are indicated for the treatment of primary hyperlipidemia, either as monotherapy or in combination with statins, and are also used to improve glycemic control in patients with type 2 diabetes mellitus.

Dosing and Administration

The typical dosing for bile acid sequestrants includes:

• Cholestyramine: 8-16 g/day orally divided into 2 doses
• Colestipol: 2-16 g/day orally given once or in divided doses
• Colesevelam: 6 tablets (3.75 g) once daily or 3 tablets (1.875 g) twice daily, taken with a meal and liquid

Efficacy and Safety

Bile acid sequestrants have been shown to effectively reduce LDL cholesterol by 15-30% and have a favorable safety profile, with common side effects including constipation, dyspepsia, and nausea. However, they can interfere with the absorption of many medications and fat-soluble vitamins, so they should be taken at least 4 hours apart from other medications.

Clinical Considerations

When prescribing bile acid sequestrants, clinicians should consider the potential for drug-drug interactions, GI side effects, and the inconvenience of preparation of oral suspension preparations. Additionally, the effects of colesevelam and colestipol on cardiovascular morbidity and mortality have not been determined, and CV outcomes data are limited to cholestyramine, which has been shown to reduce the risk of definite CHD death and/or definite nonfatal MI by 19% in the LRC-CPPT trial 1.

Key Points

• Bile acid sequestrants are a reasonable addition to statin therapy in high-risk patients
• They effectively reduce LDL cholesterol by 15-30%
• Common side effects include constipation, dyspepsia, and nausea
• They can interfere with the absorption of many medications and fat-soluble vitamins
• CV outcomes data are limited, but cholestyramine has been shown to reduce the risk of CHD death and/or nonfatal MI by 19% in the LRC-CPPT trial 1

From the FDA Drug Label

CLINICAL PHARMACOLOGY Cholesterol is the major, and probably the sole precursor of bile acids. During normal digestion, bile acids are secreted via the bile from the liver and gall bladder into the intestines. Bile acids emulsify the fat and lipid materials present in food, thus facilitating absorption A major portion of the bile acids secreted is reabsorbed from the intestines and returned via the portal circulation to the liver, thus completing the enterohepatic cycle. Colestipol hydrochloride binds bile acids in the intestine forming a complex that is excreted in the feces This nonsystemic action results in a partial removal of the bile acids from the enterohepatic circulation, preventing their reabsorption. Colesevelam hydrochloride is a bile acid sequestrant indicated as an adjunct to diet and exercise to: reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia

Bile Acid Sequestrants are a class of medications that bind to bile acids in the intestine, forming a complex that is excreted in the feces. This action results in a partial removal of bile acids from the enterohepatic circulation, preventing their reabsorption.

• Mechanism of Action: Bile acid sequestrants, such as colestipol hydrochloride and colesevelam hydrochloride, bind to bile acids in the intestine, forming a complex that is excreted in the feces.
• Indications: Bile acid sequestrants are indicated as an adjunct to diet and exercise to reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia and to reduce LDL-C levels in boys and postmenarchal girls with heterozygous familial hypercholesterolemia.
• Key Points:
  • Bile acid sequestrants are not absorbed and do not have a systemic effect.
  • They can increase the excretion of bile acids, which can lead to an increase in the hepatic synthesis of cholesterol.
  • The increased hepatic synthesis of cholesterol can lead to an increase in the number of low-density lipoprotein (LDL) receptors, which can result in a decrease in LDL cholesterol levels. 2, 3, 3

From the Research

Bile Acid Sequestrants

Bile acid sequestrants are a type of medication used to lower plasma lipid levels. The key points about bile acid sequestrants are:

• They are excellent agents for lowering circulating low-density lipoprotein (LDL) cholesterol levels, both alone and in combination with other lipid-lowering drugs 4
• They have been shown to lower the incidence of new coronary events and to retard the progression of coronary atherosclerosis 4
• They can induce qualitative changes in lipoproteins, which may be significant in coronary disease prevention 4
• Side effects may be bothersome for some patients, but can generally be managed effectively by modestly lowering the dosage 4

Types of Bile Acid Sequestrants

There are several types of bile acid sequestrants, including:

• Cholestyramine and colestipol, which are older agents that have been used clinically since the 1960s 4, 5
• Colesevelam, which is a newer agent that has a higher bile acid binding capacity and fewer adverse effects than other bile acid sequestrants 6, 7, 5
• Colesevelam has been shown to decrease serum LDL-C levels, improve glycemic control, and is well-tolerated, at least in short-term studies 6, 7

Efficacy and Safety

The efficacy and safety of bile acid sequestrants have been studied in several clinical trials. The key points are:

• Bile acid sequestrants can be used individually or in combination with other lipid-lowering drugs, such as statins, to lower LDL-C levels 8
• The addition of a bile acid sequestrant to a statin can produce additional LDL-C reduction, allowing many patients to reach LDL-C targets 8
• Bile acid sequestrants have excellent systemic safety profiles when used alone or in combination with other lipid-lowering drugs, although they can cause gastrointestinal side effects such as constipation and may increase plasma triglyceride levels 5