13.03.2 Statins

The levels of LDL cholesterol are commonly decreased by using the statins, which are HMG CoA reductase (hydroxyl-methylglutaryl coenzyme A-reductase) inhibitors. When the liver needs cholesterol to synthesise membranes, steroids or bile salts, it increases the number of LDL receptors. These LDL receptors are required to capture the plasma LDL cholesterol for the synthesis (Figure 13.13). One of the enzymes involved in this pathway is HMG CoA reductase. When this enzyme is inhibited, there is an increased synthesis of LDL receptors and LDL cholesterol removal from the plasma.

Figure 13.13 HMG CoA reductase (Copyright QUT, Sheila Doggrell)

Simvastatin and all the other statins were developed as inhibitors of HMG CoA reductase. Inhibition of HMG CoA reductase with a statin leads to decreased cholesterol synthesis, and increased synthesis of LDL receptors to decrease plasma LDL-cholesterol. The statins have been shown to decrease mortality and morbidity in subjects with coronary heart disease or at high cardiovascular risk e.g. diabetes. They are preferred to all other agents that have been used to decreased LDL cholesterol, as statins have a lower incidence of side effects than other agents.