What is Hyperlipidemia?

Hyperlipidemia or dyslipidemia is commonly known as high cholesterol. Cholesterol is a waxy substance that is produced by the liver and is vital for the cell formation process. Only when there is an excessive amount of cholesterol in the blood does it become potentially problematic. Hyperlipidemia, or high cholesterol, occurs when there is too much lipid (fat) in the blood.

There are three types of lipids: LDL (low-density lipoprotein cholesterol), HDL (high-density lipoprotein), and triglycerides. LDL is classified as the “bad” cholesterol. A desirable LDL level is less than 110 mg/dL, with a total cholesterol level of less than 170 mg/dL. On the other hand, HDL is known to be the “good” cholesterol. The ideal level of HDL is greater than 45 mg/dL. 

According to the Centers for Disease Control and Prevention, in 2015-2016, more than 12% of adults age 20 and older had total cholesterol higher than 240 mg/dL, and more than 18% had high-density lipoprotein (HDL) cholesterol levels less than 40 mg/dL.1 For these individuals, medication may be necessary to prevent coronary heart disease. To truly understand the role of lipid-lowering agents such as atorvastatin and rosuvastatin, let’s take a closer look at the difference in cholesterol levels to better understand this disease state.

The National Heart, Lung, and Blood Institute summarizes the cholesterol ranges in the table below^[5]

Indications for atorvastatin and rosuvastatin

Rosuvastatin and atorvastatin belong to a drug class commonly referred to as the “statins.” Statins inhibit an enzyme called 3-hydroxy-3-methyl-glutaryl-coenzyme, also known as HMG-CoA reductase. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. By inhibiting this crucial step, statins reduce cholesterol in the liver. Thus, statins are classified as HMG-CoA reductase inhibitors. They are recommended as the drug of choice for lipid-lowering therapy in patients at increased risks for cardiovascular diseases and stroke. Current guidelines also recommend statins as the lipid-lowering therapy in patients with diabetes to prevent coronary events with this patient population^[2,3].

What are the differences between atorvastatin and rosuvastatin?

Atorvastatin is commonly known and referred to by its brand name—Lipitor. Both atorvastatin and Lipitor are available in oral tablet dosage form. Available strengths are 10 mg, 20 mg, 40 mg, and 80 mg. Initial dosing for atorvastatin is typically 10 to 20 mg orally once daily or 40 mg orally once daily. After initiation of therapy, dosing is individualized within the range of 10 to 80 mg based on the patient’s lipid levels, the patient’s tolerance, and the prescriber’s clinical judgment. Both atorvastatin and Lipitor can be taken at any time of the day with or without food^[2].

The brand name of rosuvastatin is Crestor. Both rosuvastatin and Crestor are available in oral tablet and oral capsule dosage forms. The oral capsule can be opened and sprinkled on apple sauce for patients who have a problem swallowing. Available strengths are 5 mg, 10 mg, 20 mg, and 40 mg. Initial dosing is 10 to 20 mg orally once daily. The maintenance dose is typically 5 to 40 mg orally once daily. The 40 mg dose is reserved for patients who do not achieve the LDL goal with the 20-mg dose^[3].

One significant difference between atorvastatin and rosuvastatin is their metabolism pathway. Atorvastatin is metabolized extensively in the liver by CYP3A4 – an enzyme that resides in the liver and gastrointestinal tract^[2]. CYP3A4 is responsible for the metabolism of numerous medications. On the contrary, rosuvastatin’s metabolism is metabolized by the 2C9 enzyme and minimally affected by CYP3A4.3 As a result of this, rosuvastatin is objected to fewer drug and food interactions compared to atorvastatin. It is crucial to inform your healthcare providers about any new medications, over-the-counter products, or herbal supplements when taking atorvastatin or rosuvastatin.

As mentioned previously, both atorvastatin and rosuvastatin are approved by the FDA as first-line lipid-lowering therapies for adults. One unique fact about these two agents is that they are both approved to treat pediatric familial hypercholesterolemia, a genetic, life-threatening condition that causes elevated LDL and low HDL.

Should grapefruit juice be avoided while you are taking statins?

Grapefruit and grapefruit juice are favored due to their fragrant, tasty flavor and high content of vitamin C and fiber. You might have been told by a family member or a friend about staying clear of grapefruit juice or grapefruit products if you are on statin therapy, but that is not entirely true. Grapefruit is considered a CYP3A4 inhibitor, meaning that grapefruit or its juice reduces the activity of CYP3A4. As a result, some of the statins, such as atorvastatin, stay in the body longer causing increased side effects and toxicity. On the other hand, rosuvastatin or Crestor is minimally affected by CYP3A4. Therefore, it is acceptable to incorporate grapefruit juice or grapefruit in your diet if you are about to take rosuvastatin. If you are a grapefruit fan and unable to switch to a statin that is less affected by grapefruit, it is acceptable to consume a small serving of grapefruit apart from the statin administration time. Keep in mind that it’s even safer to eat a quarter or half of a grapefruit since it would take several grapefruits to make one glass of grapefruit juice. To ensure the most efficacy and safety, always check with your doctor or pharmacist about grapefruit consumption and how that will affect your medication regimen. The chart below indicates the effect of grapefruit on different statin therapy^[4].

Rosuvastatin versus atorvastatin: Which agent is a better choice?

There is no substantial evidence from clinical trials for all statins to demonstrate that one agent is more efficacious than the other. The FDA approves both atorvastatin and rosuvastatin to treat hypercholesterolemia and hyperglyceridemia in adults and their role in reducing the risk of coronary events such as heart attack and stroke. Both agents are indicated for the treatment of familial hypercholesterolemia for pediatric patients.

Regarding the safety of rosuvastatin, it may have advantages over atorvastatin due to being minimally affected by CYP3A4 causing fewer drug and food interactions.

Statin dosing is classified into low-intensity, moderate-intensity, and high intensity. Low-intensity statins’ LDL (low-density lipoprotein) lowering is less than 30%, moderate-intensity statins’ LDL lowering is between 30-50%, while high-intensity statins are expected to reduce LDL at 50% or higher^[5].

Common side effects

Atorvastatin’s common side effects include diarrhea, musculoskeletal or muscle pain, in addition to increased risk of upper respiratory tract infection and urinary tract infection. Rosuvastatin’s common side effects are abdominal pain, nausea, muscle pain, and headache. Muscle pain and an upset stomach are common side effects of statins. Please discuss any side effects you might experience with your healthcare providers since dosing and alternative options can be tailored based on your health status, tolerance, and personal preference.

Use in pregnancy, lactation, and pediatric population

Both atorvastatin and rosuvastatin show evidence of fetal and infant risks, so their use during pregnancy and lactation are contraindicated. The use of these two agents is only approved for familial hypercholesterolemia in pediatric patients.

Key points

• Atorvastatin and rosuvastatin have similar efficacy and side effect profiles
• Both medications are contraindicated during pregnancy and lactation. If you are taking atorvastatin or simvastatin and have a plan to be pregnant soon, please discuss with your doctor for discontinuation and tips on non-pharmacological alternatives such as physical activities and dietary changes.
• Rosuvastatin capsules can be opened and sprinkled on applesauce or vanilla/chocolate pudding; please swallow, and do not chew. Swallow the drug/food mixture within 60 minutes and do not store it for future use.
• Please minimize the amount of grapefruit consumed with atorvastatin. You can be more liberal with grapefruit consumption if you are or about to take rosuvastatin. Please reach out to your doctor or pharmacist if you have any questions regarding the recommended serving of grapefruit.
• Please report any signs or symptoms of muscle pain or aches, especially when accompanied by fever or malaise
• Be familiar and recognize the signs and symptoms of liver injury, including jaundice (yellow of the skin and the white of the eyes), nausea, vomiting, disorientation, confusion, and ascites (swelling of the abdomen).

Reference:

1. https://www.cdc.gov/cholesterol/facts.htm

2. https://www-dynamed-com.gcsom.idm.oclc.org/drug-monograph/atorvastatin#GUID-A0A2F386-F748-4941-9E82-E282132756BF

3. https://www-dynamed-com.gcsom.idm.oclc.org/drug-monograph/rosuvastatin#GUID-9403656F-54BB-4F0C-92A6-B6C05D35DD6F

4. https://www.health.harvard.edu/heart-health/grapefruit-juice-and-statins

5. https://www.nhlbi.nih.gov/health-topics/blood-cholesterol 

6. https://pharmacist.therapeuticresearch.com/Content/Segments/PRL/2016/Jul/Statin-Dose-Comparison-9914