Description

Ezetimibe and Atorvastatin is a combination medication used to treat high cholesterol and triglyceride levels in the blood. It is often prescribed as an adjunct to diet and exercise when those lifestyle changes alone are insufficient, or when a patient is not adequately controlled with a statin alone. This combination is particularly effective because the two drugs have complementary mechanisms of action, addressing cholesterol from different angles.

Indication

This medication is indicated for:

• Primary (heterozygous familial and non-familial) hypercholesterolemia: To reduce elevated levels of total cholesterol (Total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C).
• Mixed hyperlipidemia: For patients with this condition, often in combination with fenofibrate.
• Homozygous familial hypercholesterolemia (HoFH): Used as an adjunct to diet and other treatments (e.g., LDL apheresis) to reduce elevated Total-C and LDL-C levels.
• Prevention of cardiovascular events: It is indicated to reduce the risk of events like heart attack and stroke in patients with coronary heart disease (CHD) and a history of acute coronary syndrome (ACS).

Mechanism of Action

The combination of Ezetimibe and Atorvastatin works through two distinct and complementary pathways to lower cholesterol:

1. Ezetimibe

• Mechanism: Ezetimibe is a cholesterol absorption inhibitor. It acts on the brush border of the small intestine by selectively blocking the Niemann-Pick C1-Like 1 (NPC1L1) protein. This protein is responsible for the intestinal absorption of cholesterol from both dietary sources and bile.
• Effect: By blocking NPC1L1, ezetimibe prevents cholesterol from being absorbed into the body. This leads to a decrease in the delivery of cholesterol from the intestine to the liver. As a result, the liver’s cholesterol stores are reduced, which triggers an increase in the clearance of cholesterol from the blood.

2. Atorvastatin

• Mechanism: Atorvastatin is an HMG-CoA reductase inhibitor, a class of drugs commonly known as statins. It works by inhibiting the enzyme HMG-CoA reductase, which is the rate-limiting step in the body’s own cholesterol synthesis pathway.
• Effect: By inhibiting this enzyme, atorvastatin reduces the liver’s production of cholesterol. This decrease in intracellular cholesterol causes the liver to increase the number of LDL receptors on the surface of its cells. These receptors then capture and remove more LDL (“bad”) cholesterol from the bloodstream, leading to a significant reduction in circulating LDL-C.

By combining these two drugs, the medication provides dual inhibition of both cholesterol absorption from the gut and cholesterol synthesis in the liver, leading to a more pronounced and effective reduction in lipid levels than either drug alone.