Bile acids are synthesized in the liver and secreted into the intestinal lumen. Most bile acids are reabsorbed (enterohepatic circulation). At the highest daily dose of 24 g cholestyramine, 20 g colestipol, or 4.5 g colesevelam, an LDL-C reduction of 18 to 25% has been observed. In clinical studies, bile acid sequestrants have significantly contributed to demonstrating the effectiveness of LDL-C lowering in reducing cardiovascular (CV) events in patients with hypercholesterolemia, with the benefit being proportional to the degree of LDL-C reduction. However, these studies were conducted before many of today’s treatment options were available. Gastrointestinal side effects (most commonly flatulence, constipation, digestive disorders, and nausea) frequently occur with these drugs, even at low doses, which limits their practical use.

These adverse effects can be mitigated by starting treatment with a low dose and ensuring sufficient fluid intake. Long before the era of statins, these studies already provided evidence that risk prevention is not an effect of statins themselves but is caused by LDL-C reduction. Anion exchange resins interrupt the enterohepatic cycle and lead to the excretion of bile acids. The liver then produces more bile acids from cholesterol. The increased breakdown of cholesterol leads to a compensatory increase in LDL receptor activity. More LDL-C is removed from the circulation, resulting in a decrease in plasma LDL-C levels.

Dosages of Anion Exchange Resins

The anion exchange resin cholestyramine is one of the oldest agents for lowering LDL-C. Colesevelam is a newer bile acid sequestrant, which can also be used as monotherapy or in combination with a statin or ezetimibe in hypercholesterolemia. They have no effect on HDL-C but may increase triglycerides in some patients.

Long before statin therapy, studies had already demonstrated the protective cardiovascular effect of LDL-C reduction by anion exchange resins.

Drug Interactions

Anion exchange resins interact gastrointestinally with many other medications, so they should be taken four hours before or one hour after other medications. If the treatment goal is not achieved, a combination therapy of a statin with an anion exchange resin may be attempted.