Options for Treatment of High Cholesterol

Medications for High Cholesterol:  Hypercholesterolemia

Buildup of cholesterol and fats along the walls of the blood vessels (a process known as atherosclerosis) decreases blood flow, which decreases the oxygen supply to the heart, brain, and other parts of the body. Lowering blood levels of cholesterol and fats may help reduce this buildup and may decrease your chances of developing heart conditions such as angina (chest pain), strokes, and heart attacks.

The best thing that you can do to avoid a heart attack and stroke is keep your cholesterol low and your blood pressure stable with a goal of less than 130/80.

All of your medicines to lower cholesterol will be more effective if you actually take your medication ;-)

There are several classes of drugs used to decrease cholesterol.

These include:

1. Statins

Atorvastatin (Lipitor) 10 to 80 mg daily

Fluvastatin (Lescol, Lescol XL) 20 to 80 mg daily (or split twice daily)

Lovastatin (Mevacor, Altoprev) 20 to 80 mg daily

Pitavastatin (Livalo, Zypitamag) 2 to 4 mg daily

Pravastatin (Pravachol) 10 to 80 mg daily

Rosuvastatin (Crestor) 5 to 40 mg daily

Simvastatin (Zocor) 5 to 40 mg daily

Statins are one of the better known types of cholesterol-lowering drugs. Statins decrease cholesterol output by blocking the HMG CoA reductase enzyme that the liver uses to make cholesterol. Statins are also called HMG CoA reductase inhibitors.

Statins also:

1. Improve the function of the lining of the blood vessels.

2. Reduce inflammation (swelling) and damage.

3. Reduce the risk of blood clots by stopping platelets from sticking together.

4. Make plaques (fatty deposits) less likely to break away and cause damage.

5. These additional benefits help prevent coronary vascular disease (CVD) in people who have had events like heart attacks and in people who are at risk.

Like any other drugs, statins may produce unwanted side effects. These may include:

1. Constipation or nausea.

2. Headaches and cold-like symptoms.

3. Sore muscles, with or without muscle injury************* (This is the one that people hate)

4. Liver defects

5. Increased blood glucose levels

6. Reversible memory issues

If you’re unable to take statins because of the side effects, you’re said to be "statin-intolerant." If you are taking a statin, you should AVOID grapefruit products because they can increase side effects. You should limit the amount of alcohol that you drink because combining alcohol and statin usage can increase your risk of liver damage. Sorry.

I was at a cocktail party (not taking a statin...) and cornered a cardiologist who explained to me that statins work differently than other types of drugs. In most cases, with a prescription medication, we want you on the lowest dose that controls the problem. However, with a statin, the higher the dose you are on, the better protection that it affords. So what I do when I initially start someone on a statin is to start them on the lowest dose. I usually prescribe Atorvastatin. So for Atorvastatin, I start people on 10 mg a day and tell them to up the dosage slowly. 

What does that mean? Well, every 2-4 weeks, increase the dose by 10 mg. The highest dose of Atorvastatin is 80 mg. So...try to slowly increase to 80 mg if you tolerate it.  I would be happy if you could take 40 mg/day.

What would make you not tolerate it? Well, muscle aches, constipation, nausea, headaches, cold-like symptoms, or if your labs become abnormal. 

Because statins can cause liver failure, we check your liver function tests every 6 months at the latest. Usually, we start at every 3 months to make sure there are no problems. I only give 6 months of statin prescription at a time, so if you need a refill, you have to come in for labs first. This is the one medication that you cannot have a refill if you do not come in and get your labs done. 

If you have a stroke or heart attack and and go to the hospital...and live, you come out of the hospital with a prescription for atorvastatin 80 mg to take every day. Once you have a stroke or heart attack, you don't really have a choice about your statin dosage. I would rather that you work your way up to a dosage that is good for you to prevent a heart attack or stroke. 

People are more likely to take their statins if they have no side effects...so...I would rather you take a dose that you WILL take daily that causes NO side effects than prescribe a high dose that makes you feel terrible and you don't take it...Right? The medication only works if you take it regularly.

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2. PCSK9 inhibitors

Alirocumab (Praluent) Initially 75 mg once every 2 weeks or 300 mg every 4 weeks

Evolocumab (Repatha) 140 mg every 2 weeks or 420 mg once a month by injection.

PCSK9 inhibitors are designed to attach to a particular liver protein, which results in lowered LDL cholesterol. This class of drug can be given WITH STATINS and is usually for people at HIGH RISK of heart disease who have not been able to lower their cholesterol enough through other means.

What are some possible side effects of PCSK9 inhibitors?

Possible side effects include pain, including muscle pain (myalgia) and back pain, or swelling at the injection site and cold-like symptoms. Another drawback may be cost as these products may be expensive.

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3. Fibric acid derivatives (also called fibrates)

Fenofibrate (Tricor, Antara, Fenoglide, Fibricor, Lipidil, Lipofen, Triglide, Trilipix)

(doses vary)

Gemfibrozil (Lopid) 600 mg twice daily. Take 30 minutes before breakfast & dinner.

***********Gemfibrozil should not be taken with statins***************

Fibric acid derivatives make up another class of drugs that reduce blood lipid (fat) levels, especially triglycerides. Triglycerides are fats that come from food that are created when you consume calories that are not spent.

Fibric acid derivatives may also increase the level of HDL, also called the “good” cholesterol, while lowering liver production of LDL, the “bad” cholesterol. People who have severe kidney disease or liver disease should not take fibrates.

Possible side effects of fibrates include:

1. Constipation or diarrhea.

2. Weight loss.

3. Bloating, belching or vomiting.

4. Stomachache, headache or backache.

5. Muscle pain and weakness.

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4. Bile Acid Sequestrants (also called bile acid resins)

Cholestyramine (Questran) 

Colestipol (Colestin) 

Colesevelam (Welchol®) 

Bile acid sequestrants (also called bile acid resins)

This class of drugs works inside the intestine by attaching themselves to bile, a greenish fluid made of cholesterol that is produced by the liver to digest food. The binding process means that less cholesterol is available in the body. Resins decrease LDL cholesterol and give a slight boost to HDL cholesterol levels.

What bile acid resins are available to treat cholesterol?

1. Cholestyramine (Questran®) 4 – 16 g/day (once or twice daily). The dose of 4 grams one to two times per day should be increased gradually over about one month intervals to 8-16 g/day divided into two doses. The maximum dose is 24 g/day taken in divided doses.

2. Colestipol (Colestid®) Granule formulation: 5 g once or twice a day increase by 5 g every 1 to 2 months if needed. Maintenance dose: 5 to 30 g/day once daily or in divided doses.

Tablet formulation: 2 g once or twice a day increase by 2 g once or twice daily every 1 to 2 months if needed. Maintenance dose: 2 to 16 g/day once daily or in divided doses.

3. Colesevelam (Welchol®) 3.75 g/day in one to two divided doses. Product comes in tablet or powder form.

Possible side effects of bile acid sequestrants include:

1. Sore throat, stuffy nose.

2. Constipation, diarrhea.

3. Weight loss.

4. Belching, bloating.

5. Nausea, vomiting, stomach pain.

If your medication is a powder, never take it dry. It must always be mixed with at least three to four ounces of liquid such as water, juice or a NON-carbonated beverage.

If you take other medications besides these, make sure you take the other drugs one hour before or four hours after taking the bile acid resin.

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5. Nicotinic acid (also called niacin).

Nicotinic acid, also called niacin, is a B-complex vitamin. You can get over-the-counter versions of this, but some versions are prescription only. Niacin decreases LDL cholesterol and triglycerides and increases HDL. 

***********If you have gout or severe liver disease, you should not take niacin***************

What nicotinic acid products are available to treat cholesterol levels?

1. Extended release niacin (Niaspan®) 1-2 g/day once daily at bedtime.

2. Immediate release niacin (Niacor®) 1.5-3 g/day (divide daily dose up to to three times per day).

3. Sustained release (Slo-Niacin®) or 

4. Over-the-counter niacin products. Take 250-750 mg once per day, morning or evening or as directed. 

What are possible side effects of niacin?

The main side effect of niacin is flushing of the face and upper body, which might be lessened if you take it with meals. You might have less flushing if you take aspirin about 30 minutes before taking niacin.

Other side effects include:

1. Skin issues, such as itching or tingling.

2. Headache.

3. Stomach upset.

4. Can lead to increased blood sugars.

5. Coughing.

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6. Selective cholesterol absorption inhibitors

ZETIA (See #8 also)

Cholesterol absorption inhibitors reduce the absorption of dietary and biliary cholesterol through the intestines. Therefore it deceases the amount of intestinal cholesterol that is delivered to the liver. Reduced levels of cholesterol delivered to the liver which leads to increased clearance of LDL cholesterol.

Ezetimibe, or Zetia, is used together with lifestyle changes (diet, weight-loss, exercise) to reduce the amount of cholesterol (a fat-like substance) and other fatty substances in the blood. It may be used alone or in combination with an HMG-CoA reductase inhibitor (statin). Ezetimibe is in a class of medications called cholesterol-lowering medications. It works by preventing the absorption of cholesterol in the intestine.

1. Ezetimibe is available at a single dose of 10 mg daily and lowers LDL cholesterol levels by 18%–25%, with no effect on other components of the lipid profile. 

The combination of a statin and ezetimibe can lower LDL cholesterol by ∼70%.Compared to Bile Acid sequestrants and niacin, ezetimibe is well tolerated with minimal side effects. At this time, ezetimibe should still be considered as a second-line drug added to statin therapy when LDL cholesterol targets have not been reached or when statins cannot be tolerated as first-line therapy.

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7. FISH OILS

Omega-3 fatty acid esters and polyunsaturated fatty acids (PUFAs)

These kinds of drugs, used to lower triglycerides, are commonly called FISH OILS. Some products are available as OTC items, while others are prescription only. 

Here are two things to consider: 

1. Fish oils might interfere with other medications, and 

2. Some people are allergic to fish and shellfish.

What omega-3 products are available to treat cholesterol levels?

1. Icosapent ethyl (Vascepa®) 2 g twice daily with meals.

2. Omega-3-acid ethyl esters (Lovaza®) 2 g twice daily.

What are the possible side effects of omega 3 products?

1. Belching.

2. Skin issues like rash or itching.

3. Gas.

4. Fishy taste.

5. Increased bleeding time.

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8. Adenosine triphosphate-citrate lyase (ACL) inhibitors

The FDA has approved bempedoic acid (Nexletol™) to lower cholesterol. Bempedoic acid works in the liver to slow down cholesterol production. The medication comes in 180-mg tablets taken once per day with or without food. It should be taken with statin medications, but there are dosage limitations if taken with simvastatin or pravastatin.

What are the possible side effects of bempedoic acid?

1. Upper respiratory infection.

2. Stomach, back or muscle pain.

3. Increased levels of uric acid.

4. Tendon injury.

This is a new drug for cholesterol that you take IN ADDITION to a statin that is called Nexlizet. Here is the link to the website:

https://www.nexlizet.com

Nexlizet is an adenosine triphosphate-citrate lyase (ACL) inhibitor and a cholesterol absorption inhibitor, is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C. 

(It is a new drug and there is a copay card on the website, so it must be expensive. It may be worth a try for those of you who cannot take a high dosage of a statin. Especially those of you who I am worried about...you know who you are...Let me know if you would like to try it.)

It is indicated for people already on a statin that cannot get their LDL levels down. One tablet of NEXLIZET contains 180 mg of bempedoic acid and 10 mg of ezetimibe.

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9. Red Rice Yeast (Mevacor) 

or Plant Stanols (CholestOff and Benecol)

Many people say they prefer to take ‘natural’ medicines over prescription drugs. However, just because something is natural doesn’t mean that it’s safe. In the U.S., supplements are not regulated as closely as medicines. Supplements can also interfere in dangerous ways with medications that you already take.

However, red rice yeast extract does contain lovastatin, which is the same chemical that is in Mevacor. 

Plant stanols are another nonprescription choice for lowering cholesterol. Plant stanols work by stopping the body from absorbing cholesterol in the intestines. One brand is CholestOff® capsules, while plant stanols are also available in margarine substitutes like Benecol®.

Author

Pamela Gaudry, MD Dr. PAMELA GAUDRY is a board certified OB/GYN who provides her patients their primary care. She is a certified sex therapist and has special training in menopausal management. She is located in Savannah, GA and is the owner and founder of The Georgia Center for Menopausal Medicine and Direct Primary Care.