What is the first line of treatment for hypercholesterolemia in adults?

From the Guidelines

The first line of treatment for hypercholesterolemia in adults is lifestyle modifications, followed by statin therapy as the primary pharmacological treatment, as recommended by the most recent guidelines 1.

Key Components of Lifestyle Modifications

• Adopting a heart-healthy diet low in saturated fats and trans fats, rich in fruits, vegetables, whole grains, and lean proteins
• Regular physical activity of at least 150 minutes of moderate-intensity exercise per week
• Weight loss for overweight individuals
• Smoking cessation
• Limiting alcohol consumption

Statin Therapy

• Statins are the first-line pharmacological treatment for hypercholesterolemia in adults
• Common statins include atorvastatin (10-80 mg daily), rosuvastatin (5-40 mg daily), and simvastatin (10-40 mg daily)
• Statins work by inhibiting HMG-CoA reductase, an enzyme crucial for cholesterol synthesis in the liver, thereby reducing LDL cholesterol levels by 20-60%

Treatment Goals

• Individualized based on cardiovascular risk factors, with target LDL levels varying accordingly
• For patients at very high CV risk, an LDL-C goal of < 1.8 mmol/L (70 mg/dL), or a reduction of at least 50% if the baseline LDL-C is between 1.8 and 3.5 mmol/L (70 and 135 mg/dL) is recommended 1
• Regular monitoring of lipid levels and liver function is necessary to assess treatment efficacy and detect potential side effects

Additional Considerations

• Combination therapy employing statins and fibrates or niacin may be necessary to achieve lipid targets, but have not been evaluated in outcomes studies for either event reduction or safety 1
• Lipoprotein(a) is another emergent target for PCSK9 inhibitors, and measuring Lp(a) in patients at high risk of cardiovascular disease (CVD) is recommended, with a target level below 50 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 low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia.

The first line of treatment for hypercholesterolemia in adults is typically lifestyle modifications and statin therapy.

• Statin therapy is recommended as the first line of treatment for adults with hypercholesterolemia, with the goal of reducing LDL-C levels.
• The choice of statin and dosage depends on the individual patient's risk factors, LDL-C levels, and other factors, as outlined in the drug labels for atorvastatin 2 and rosuvastatin 3.
• Lifestyle modifications include a healthy diet, regular exercise, weight management, and avoidance of tobacco products. It is essential to assess the patient's individual risk factors and LDL-C levels to determine the best course of treatment.

From the Research

First Line Treatment of Hypercholesterolemia in Adults

The first line treatment of hypercholesterolemia in adults typically involves the use of statins, which are powerful lipid-lowering agents that reduce cardiovascular-related morbidity and mortality 4, 5. However, some patients may not be able to attain target low-density lipoprotein cholesterol (LDL-C) levels despite receiving maximally tolerated doses of high-intensity statins, and may require alternative treatments 6.

Statin Monotherapy vs. Ezetimibe-Statin Combination

Some studies suggest that an ezetimibe-statin combination may be more effective in reaching LDL-C goals than statin monotherapy, especially in patients at high or very high cardiovascular risk 7, 8. The combination of ezetimibe and a statin, such as rosuvastatin, has been shown to be safe and effective in patients with hypercholesterolemia or dyslipidemia, with or without diabetes and with or without cardiovascular disease 4, 8.

Key Points to Consider

• Statins are the cornerstone of hypercholesterolemia treatment, but may not be sufficient for all patients 5
• Ezetimibe-statin combination may be more effective in reaching LDL-C goals than statin monotherapy 7, 8
• Rosuvastatin and ezetimibe combination has been shown to be safe and effective in patients with hypercholesterolemia or dyslipidemia 4, 8
• Alternative treatments, such as PCSK9 inhibitors and bempedoic acid, may be considered for patients who cannot tolerate statins or require additional LDL-C lowering 6