Oral Cholesterol Lowering Drugs

Hypercholesterolaemia

Cholesterol is a fat-like substance found in your body and it is mainly made by the liver or absorbed via food intake. Being insoluble in water, cholesterol binds to proteins to become lipoproteins so that it can be transported in blood. There are different types of lipoprotein cholesterol, depending on the proportion of cholesterol, triglyceride, etc. the lipoprotein carries. Two most commonly known types of lipoprotein cholesterol are:

• High-density lipoprotein (HDL) cholesterol– also known as “good cholesterol”. It carries excess cholesterol back to the liver for degradation or excretion.


• Low-density lipoprotein (LDL) cholesterol- LDL cholesterol or “bad cholesterol” carries cholesterol around your body. Excess cholesterol will build up in the walls and clog the arteries.

Whilst cholesterol is essential for building cells and producing hormones in the body, having high level of bad cholesterol in your blood (hypercholesterolaemia) can increase your risk of developing cardiovascular diseases, e.g. heart attack or stroke. Thus, maintaining your cholesterol level at healthy level can reduce your risk of developing cardiovascular diseases.

There are many factors associated with high blood cholesterol which include older age, unhealthy diet, obesity, lack of exercise, drinking excessive amount of alcohol, smoking and family history of hypercholesterolaemia. Furthermore, some kidney and liver diseases or underactive thyroid glands can also raise blood cholesterol levels. Patients suffering from hypercholesterolaemia usually have no symptoms and a simple blood test can confirm the diagnosis.

Treatment

The aim of treatment for hypercholesterolaemia is not merely to lower your cholesterol level but also to control your risk of developing cardiovascular diseases. For patients who have high blood cholesterol, if you do not have heart disease or secondary causes for hypercholesterolaemia, you will usually be advised to make lifestyle changes first such as regularly exercising more and eating a healthier diet. If your cholesterol level does not improve after a few months and your estimated risk of developing cardiovascular diseases is high, your doctor may recommend you to take cholesterol lowering drugs in addition to dietary and lifestyle modifications.

Cholesterol Lowering Drugs

In Hong Kong, most cholesterol lowering drugs can only be obtained from pharmacy with a prescription. They should be used under close supervision by healthcare professionals. Commonly used cholesterol lowering drugs include statins, fibrates, bile-acid binding resins, ezetimibe and nicotinic acid.

1. Statins (e.g. lovastatin, simvastatin, atorvastatin, rosuvastatin)

Statins reduce the production of cholesterol by the liver and this causes your liver to absorb cholesterol from your blood. They are generally considered to be the most effective type of cholesterol lowering drugs. Statins may also be used to reduce your risk of developing cardiovascular diseases.

Statins may affect liver function. If you have liver disease or persistently abnormal liver function tests, you should not take statins. Before you start taking a statin, your doctor may order a blood test to ensure your liver function is normal. These tests may be repeated regularly whilst you are taking these medicines to monitor your liver function. Furthermore, statins may cause inflammation and damage to your muscles, especially if they are given at a high dose or in conjunction with certain drugs such as itraconazole, ketoconazole, erythromycin, gemfibrozil, etc. There could also be muscle pain; and in rare cases, there could be serious and acute manifestation of the muscle damage (e.g. rhabdomyolysis). You should always follow the dosage recommended by your healthcare professionals and report any symptoms to your doctors.

Lovastatin is one of the earliest marketed statins. It was synthesized chemically and marketed as a western medicine to reduce blood cholesterol in the 80’s. However, it was later found that its chemical structure is the same as a compound called monacolin K found in red yeast rice. Red yeast rice (abbreviated: RYR; sometimes known as: red fermented rice; Chinese name: 红麴米/红麴/红曲/赤曲/丹曲, is obtained by fermenting rice with some kinds of fungi (e.g. Monascus purpureus). After fermentation, many active natural substances will be produced in the RYR, including monacolin K (shown in the figure) which is an active substance with a lipid lowering potency. In other words, the RYR contains lovastatin (i.e. monacolin K); but as the amount of lovastatin in the RYR varies significantly, it is not recommended as a medicine for treating hypercholesterolaemia.

If your blood lipid level cannot be controlled by statins, addition of other cholesterol lowering drug may be needed but close medical supervision is required because of possible drug interactions.

2. Bile-acid binding resins (e.g. colestyramine)

The body makes bile acids by breaking down LDL cholesterol. Bile-acid binding resins lower LDL cholesterol by combining with bile acids, preventing their intestinal reabsorption, so that your liver needs to break down cholesterol from your blood to produce bile acids.

3. Ezetimibe

Ezetimibe blocks the intestinal absorption of dietary cholesterol into your blood, thus lowering your cholesterol level. It is used as an adjunct to dietary modification in patients with primary hypercholesterolaemia and patients with homozygous familial hypercholesterolaemia in combination with a statin.

4. Fibrates (e.g. bezafibrate, fenofibrate, gemfibrozil)

Fibrates reduce triglycerides and increases level of HDL cholesterol in your blood. They are used mainly in patients with hypertriglyceridaemia. Patients with hypercholesterolaemia can change to take fibrates when a statin is contraindicated or not tolerated.

5. Nicotinic acid

Nicotinic acid decreases LDL cholesterol whilst increases HDL cholesterol levels in your blood. However, its clinical use is limited by the side effects of vasodilatation and possible risk of liver damage with long term use.

General advice on taking cholesterol lowering drugs

• Cholesterol lowering drugs (e.g. statins, fibrates, ezetimibe, nicotinic acid) are prescription medicines and should only be purchased with a doctor’s prescription and taken as directed by your doctor.

• Be familiar with the name and dosage of the drugs you are taking. Be cautious about their possible side effects.

• Cholesterol lowering drugs are normally to be taken in the evening.

• RYR, presented as food supplement, may contain variable amount of the substance lovastatin. Be aware of its add-on effect on medications (including on other statins) such as the development of any signs of muscle pain.

• Have regular tests for the cholesterol and liver function as prescribed by your doctor.

• Seek your doctor’s advice on the best treatment option. There are many types of cholesterol lowering drugs with different actions and side effect profiles; your doctor will use the most appropriate drugs after considering your condition and your response to the drugs.


• Inform your doctor of your medical history and the drugs you are taking because other drugs may interact with cholesterol lowering medications and some disease may warrant special precautionary measures.

• Inform your doctor that you are pregnant or breast feeding as some types of cholesterol lowering drugs should not be taken by women who are pregnant or breast feeding.

• Seek medical advice as soon as possible if you experience any side effects suspected to be related to your cholesterol lowering drugs, such as muscle pain, tenderness and weakness.

• Have regular follow-ups as advised by your doctor.