What is the treatment for hypercholesterolemia (high cholesterol)?

From the Guidelines

Hypercholesterolemia should be treated with a combination of lifestyle modifications and medication, with statins being the first-line therapy, aiming to reduce LDL-C levels to < 1.8 mmol/L (70 mg/dL) in very high-risk patients or < 2.6 mmol/L (100 mg/dL) in high-risk patients, as recommended by the 2016 ESC/EAS guidelines 1. To achieve this, patients should start with dietary changes, reducing saturated and trans fats, and increasing fiber intake through fruits, vegetables, and whole grains. Regular exercise of at least 150 minutes per week of moderate activity helps lower cholesterol levels. Weight loss, if overweight, and smoking cessation are also crucial.

• Key lifestyle modifications include:
  • Dietary changes to reduce saturated and trans fats
  • Increased fiber intake through fruits, vegetables, and whole grains
  • Regular exercise of at least 150 minutes per week of moderate activity
  • Weight loss, if overweight
  • Smoking cessation If lifestyle changes are not sufficient, medications may be prescribed, with statins being the primary choice, as stated in the 2020 position paper of the European Society of Cardiology 1.
• Medication options include:
  • Statins, such as atorvastatin (10-80mg daily) or rosuvastatin (5-40mg daily)
  • Ezetimibe (10mg daily) for patients who cannot tolerate statins or need additional cholesterol lowering
  • PCSK9 inhibitors (evolocumab or alirocumab by injection every 2-4 weeks) for further cholesterol reduction Treatment goals depend on individual cardiovascular risk, with higher-risk patients requiring more aggressive therapy, as outlined in the 2016 ESC/EAS guidelines 1. Regular monitoring of lipid levels and liver function is essential during treatment. These interventions work by either reducing cholesterol production in the liver, increasing cholesterol removal from the bloodstream, or blocking intestinal cholesterol absorption, ultimately reducing the risk of atherosclerosis and cardiovascular events.

From the FDA Drug Label

To reduce the risk of: ... As an adjunct to diet to reduce low-density lipoprotein (LDL-C) in: Adults with primary hyperlipidemia As an adjunct to diet for the treatment of adults with: Primary dysbetalipoproteinemia. Hypertriglyceridemia. Treatment for hypercholesterolemia involves using atorvastatin as an adjunct to diet to reduce low-density lipoprotein (LDL-C) in adults with primary hyperlipidemia 2.

• The recommended approach is to use atorvastatin in conjunction with diet to reduce LDL-C levels.
• Key considerations include the patient's overall risk factors for coronary heart disease (CHD) and the presence of other conditions such as type 2 diabetes mellitus or heterozygous familial hypercholesterolemia.

From the Research

Treatment Options for Hypercholesterolemia

• Lifestyle modifications, including changes in diet, exercise, reduction in body mass index, and abstinence from alcohol consumption, can be effective in managing hypercholesterolemia, particularly in cases with elevated triglycerides 3
• Pharmacotherapy with fibrates and statins can be used as a secondary intervention for managing hypercholesterolemia, especially in cases with triglycerides ≥ 10 mmol/L 3
• Statin alternatives, such as ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and bempedoic acid, can be used for patients who are unable to tolerate statins or require additional treatment 4, 5, 6
• PCSK9 inhibitors, such as evolocumab and alirocumab, have been shown to be effective in reducing low-density lipoprotein cholesterol (LDL-C) levels and cardiovascular risk 4, 5, 6
• Newer medications, such as inclisiran and evinacumab, have also been developed to further lower LDL-C levels and reduce cardiovascular risk 6
• Oral PCSK9 inhibitors, such as AZD0780, are being developed as a once-daily treatment for hypercholesterolemia and have shown promising results in clinical trials 7

Pharmacological Strategies

• Ezetimibe can be used in combination with statins to further reduce LDL-C levels and decrease cardiovascular risk 5, 6
• PCSK9 inhibitors can be used in combination with maximally tolerated statin therapy to significantly decrease serum LDL-C levels and reduce cardiovascular risk 5, 6
• Bempedoic acid can be used as an alternative to statins for patients who are intolerant or require additional treatment 6
• Inclisiran can be used to reduce LDL-C levels with the advantage of only requiring 2 or 3 injections per year 6
• Evinacumab can be used to induce robust LDL-C lowering in patients with homozygous familial hypercholesterolemia or severe hypercholesterolemia 6

Clinical Trials and Safety

• Clinical trials have shown that statin alternatives and newer medications are generally well-tolerated and effective in reducing LDL-C levels and cardiovascular risk 4, 5, 6, 7
• The safety and efficacy of these medications are being continuously evaluated in ongoing clinical trials 6, 7
• The choice of treatment should be based on the individual patient's needs and medical history, as well as the cost and availability of the medication 4