Statins Colestipol

In addition to treatment with the statins, hypercholesterolemia is sometimes treated with the use of nonabsorbable anion-exchange resins like cholestyramine (5.13) and colestipol, which sequester bile acid in the intestine, excrete them, and thus increase their synthesis in the liver by a feedback mechanism. Increased bile acid synthesis increases cholesterol metabolism and also decreases LDL concentrations. Unfortunately, these resins interfere with the absorption of other fats and fat-soluble vitamins (A, D, E, and K). They... 

A statin could be considered in this patient with appropriate monitoring. Fibrates, niacin or ezetimibe could be used with appropriate monitoring of LFTs. Colestyramine/colestipol and acipimox should be safe to use. 

Pravastatin is the statin of choice in this patient as it is least likely to accumulate, is hydrophilic, and is not highly protein bound. The starting dose should be low and should be increased cautiously. Monitoring of LFTs is required. Colestyramine and colestipol may be considered and may help the patient s pruritus. Niacin and acipimox could be used if the pruritus does not worsen. The fibrates should be avoided because of the risk of gallstone formation. Ezetimibe could be considered alone. 

Statins should be avoided. If absolutely necessary, pravastatin could be used, starting at a low dose and with cautious adjustment according to clinical response. The patient s synthetic liver function should be monitored closely. In the event of the slightest deterioration of function, pravastatin should be stopped immediately. Colestyramine/colestipol should be safe to use but may cause a reduction in vitamin K absorption and increase the risk of a bleed. Constipation might induce encephalopathy. The fibrates should be avoided due to their potential effect on coagulopathy. Ezetimibe should be safe to use alone. Acipimox and niacin are gastric irritants and would be best avoided. 

The two established bUe-acid sequestrants or resins (cholestyramine and colestipol) are most often used as second agents if statin therapy does not lower LDL-C levels sufficiently. When used with a statin, cholestyramine and colestipol usually are prescribed at submaximal doses. Maximal doses can reduce LDL-C by up to 25% but are associated with unacceptable gastrointestinal (GI) side effects (bloating and constipation) that limit compliance. Colesevelam is a newer bile-acid sequestrant that is prepared as an anhydrous gel and taken as a tablet. It lowers LDL-C by 18% at its maximum dose. The safety and efficacy of colesevelam have not been studied in children or pregnant women. 

The reduction in IDL-C by resins is dose-dependent. Doses of 8-12 g of cholestyramine or 10-15 g of colestipol are associated with 12-18% reductions in LDL-C. Maximal doses (24 g of cholestyramine, 30 g of colestipol) may reduce LDDC by as much as 25%, but will cause GI side effects that are poorly tolerated by most patients. One to two weeks is sufficient to attain maximal LDDC reduction by a given resin dose. In patients with normal triglyceride levels, triglycerides may increase transiently and then return to baseline. HDL-C levels increase 4-5%. Statins plus resins or niacin plus resins can reduce LDL-C by as much as 40-60%. Colesevelam, in doses of 3-3.75 g, reduces LDL-C levels by 9-19%. 

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