ProLipid

Bile Acid Sequestrants ("Resins"): Removing Bile Acids To Deplete Cholesterol Supply

As the name suggests, bile acid sequestrants or "resins" bind bile acids. Instead of being recycled by re-uptake in the lower area of the gut, bile acids bound to sequestrants are excreted in stools. As a result, the supply of cholesterol (the raw material for bile acid) is depleted as new bile acid must be manufactured in the liver.

With bile acid sequestrants, LDL cholesterol levels can be reduced by approximately 20%. Bile acid sequestrants are not absorbed into the bloodstream, but are confined to the digestive system until excreted in stools. That's why they are considered to be especially safe without any serious side effects. Although they can interfere with the absorption of several drugs and fat-soluble vitamins such as Vitamin A, D, E and K, individuals can control this by taking other drugs several hours earlier or later and by supplementing the aforementioned vitamins.

However, patients' "compliance" (the regular, long-term intake of the drug) of bile acid seuqestrants is usually low since it can cause severe intestinal discomfort, diarrhea and sickness. In addition, several grams of sandy-textured resin must be taken daily, which adds to the high drop-out rate of patients on sequestrant therapy. An advantage of bile acid sequestrants is the fact they can be combined with other forms of cholesterol or triglyceride-lowering therapies.

A Promising New Approach: CETP Inhibitors

One of the most exiting new developments to treat lipid disorders are cholesteryl ester transfer protein (CETP) inhibitors. CETP inhibitors are not currently available on the market. However, several large pharmaceutical companies are working on this new drug class, including Pfizer (active agent: torcetrapib), Merck (active agent: anacetrapib), and Roche (drug code: R-1658).

CEPTs are liver enzymes that transfer cholesterol from HDL to LDL particles, turning "good" cholesterol into "bad" cholesterol. The primary effect of suppressing CEPTs is a significantly increased serum HDL cholesterol level. The lowering of bad LDL cholesterol is a positive side effect.

This approach has been criticized recently when Pfizer's torcetrapib failed to lower heart problems in a recent clinical trial. As an unforeseen side effect, it actuallyl raised blood pressure, thereby increasing heart problems and the overall risk of death. Although Merck pointed out that their CETP candidate anacetrapib did not increase blood pressure and Roche claimed their product's development was "on track," it is not known whether CETP inhibitors can fulfill their promise of becoming a standard treatment for patients with heart disease, as predicted only a year ago.

Special Case: Apheresis - A Non-Drug Intervention To Lower Cholesterol

Apheresis is similar to blood dialysis for patients with serious kidney damage: their blood is pumped through a machine that filters out LDL cholesterol before returning it to the patient. This method for lowering cholesterol is usually confined to severe cases that fail to respond sufficiently to drug treatment for lowering cholesterol.