What is the proper use of statins (HMG-CoA reductase inhibitors) by type and levels of hypercholesterolemia?

From the Guidelines

Statins should be prescribed based on individual cholesterol levels and cardiovascular risk factors, with high-intensity statins recommended for patients with LDL cholesterol above 190 mg/dL, and moderate-intensity statins for those with LDL between 160-189 mg/dL and additional risk factors, as supported by the 2018 American Heart Association/American College of Cardiology/Multisociety Cholesterol Guideline 1.

Statin Intensity and Dosage

The choice of statin intensity and dosage depends on the patient's LDL cholesterol level and cardiovascular risk factors.

• High-intensity statins, such as atorvastatin (40-80 mg daily) or rosuvastatin (20-40 mg daily), are typically recommended for patients with LDL cholesterol above 190 mg/dL, as they can reduce LDL-C levels by at least 50% 1.
• Moderate-intensity statins, such as atorvastatin (10-20 mg), rosuvastatin (5-10 mg), simvastatin (20-40 mg), or pravastatin (40-80 mg) daily, are often appropriate for patients with LDL between 160-189 mg/dL and additional risk factors, as they can reduce LDL-C levels by 30-49% 1.
• Low-to-moderate intensity statins, such as pravastatin (10-20 mg), lovastatin (20-40 mg), or fluvastatin (20-40 mg) daily, may be suitable for patients with LDL between 130-159 mg/dL and moderate risk, as they can reduce LDL-C levels by less than 30% 1.

Monitoring and Side Effects

Regular monitoring of lipid levels and liver function is important, usually 4-12 weeks after starting therapy and then periodically.

• Potential side effects of statins include muscle pain, liver enzyme elevations, and rarely, rhabdomyolysis, so patients should report unusual muscle pain or weakness to their healthcare provider immediately.
• The 2018 American Heart Association/American College of Cardiology/Multisociety Cholesterol Guideline recommends that statin therapy be individualized based on the patient's response to treatment and their cardiovascular risk factors 1.

Key Considerations

• The guideline suggests that addition of ezetimibe to maximally tolerated statin therapy is reasonable when LDL-C levels are 1.8 mmol/L (70 mg/dL) or higher, and that a PCSK9 inhibitor may be considered in patients at very high risk whose LDL-C levels remain above this threshold while receiving a statin plus ezetimibe therapy 1.
• The choice of statin and dosage should be based on the patient's individual needs and cardiovascular risk factors, as well as the potential for drug interactions and side effects.
• The 2018 guideline emphasizes the importance of a clinician-patient risk discussion to determine the best course of treatment for each patient 1.

From the FDA Drug Label

To reduce the risk of major adverse cardiovascular (CV) events (CV death, nonfatal myocardial infarction, nonfatal stroke, or an arterial revascularization procedure) in adults without established coronary heart disease who are at increased risk of CV disease based on age, high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L, and at least one additional CV risk factor. As an adjunct to diet to: reduce LDL-C in adults with primary hyperlipidemia. Reduce LDL-C and slow the progression of atherosclerosis in adults. Reduce LDL-C in adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH) As an adjunct to other LDL-C-lowering therapies, or alone if such treatments are unavailable, to reduce LDL-C in adults and pediatric patients aged 7 years and older with homozygous familial hypercholesterolemia (HoFH). As an adjunct to diet for the treatment of adults with: Primary dysbetalipoproteinemia. Hypertriglyceridemia. Adults( 2. 2): Recommended starting dosage is 10 or 20 mg once daily; dosage range is 10 mg to 80 mg once daily. Patients requiring LDL-C reduction >45% may start at 40 mg once daily.

The proper use of statins by type and levels of cholesterol is as follows:

• Rosuvastatin:
  • Indicated to reduce the risk of major adverse cardiovascular events in adults without established coronary heart disease who are at increased risk of CV disease.
  • Used as an adjunct to diet to reduce LDL-C in adults with primary hyperlipidemia.
  • Dosage range is not specified in the provided text for rosuvastatin.
• Atorvastatin:
  • Indicated to reduce the risk of myocardial infarction, stroke, revascularization procedures, and angina in adults with multiple risk factors for coronary heart disease.
  • Used as an adjunct to diet to reduce LDL-C in adults with primary hyperlipidemia.
  • Recommended starting dosage is 10 or 20 mg once daily; dosage range is 10 mg to 80 mg once daily.
  • Patients requiring LDL-C reduction >45% may start at 40 mg once daily 2, 2.

From the Research

Statin Types and Levels of Cholesterol

The proper use of statins by type and levels of cholesterol can be understood through various studies.

• Rosuvastatin 10 mg has been shown to reduce LDL-C levels significantly more than atorvastatin 20 mg at week 6 (44.6% vs. 42.7%, p < 0.05) 3.
• Atorvastatin 20 mg administered every other day has been found to cause a significant lipid-lowering and anti-inflammatory effects similar to that of daily administration, with a 36.1% reduction in LDL-cholesterol levels by the end of the first month (p<0.01) 4.
• Rosuvastatin 10 mg has been compared with atorvastatin 10 mg and 20 mg, simvastatin 20 mg, and pravastatin 40 mg, and has been found to be more effective in allowing patients to reach European and ATP III LDL-C goals, with consistently greater reductions in LDL-C, total cholesterol, and non-HDL-C 5.
• The use of PCSK9 inhibitors, such as evolocumab and alirocumab, in combination with statin therapy can reduce LDL-C by 50-60% above that achieved by statin therapy alone, and may reduce cardiovascular events and all-cause mortality in patients with clinical ASCVD 6.
• Atorvastatin initiated at different starting doses (10,20,40, and 80 mg) has been found to be effective and safe for the treatment of patients with dyslipidemia, with dose-dependent reductions in LDL-C levels across the 10- to 80-mg-dose range (35.7%-52.2%) 7.

Cholesterol Levels and Statin Therapy

The following cholesterol levels and statin therapy can be considered:

• LDL-C > or = 3.4 and < 5.7 mmol/L [130 and 220 mg/dL]: Rosuvastatin 10 mg or atorvastatin 20 mg can be considered 3.
• LDL-C > or = 2.99 mmol/l and triglycerides of <4.52 mmol/l: Rosuvastatin 10 mg, atorvastatin 10 mg and 20 mg, simvastatin 20 mg, and pravastatin 40 mg can be considered 5.
• Total cholesterol levels of above 200 mg/dl and LDL-cholesterol levels of above 130 mg/dl: Atorvastatin 20 mg daily or every other day can be considered 4.