What are the treatment options for hypercholesterolemia (high cholesterol)?

From the Guidelines

Treatment for high cholesterol should prioritize statin therapy as the first-line treatment, aiming for an LDL-C goal of < 1.8 mmol/L (70 mg/dL) in very high-risk individuals 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), as recommended by the 2016 ESC/EAS guidelines 1. High cholesterol management involves a combination of lifestyle modifications and medication. Lifestyle changes include adopting a heart-healthy diet low in saturated fats and trans fats, focusing on fruits, vegetables, whole grains, lean proteins, and healthy fats like olive oil. Regular exercise, aiming for 150 minutes of moderate activity weekly, weight management, smoking cessation, and limiting alcohol consumption are essential lifestyle modifications. If these changes aren't sufficient, medications may be prescribed. Statins, such as atorvastatin 10-80mg daily, rosuvastatin 5-40mg daily, or simvastatin 10-40mg daily, are the most common first-line treatment and work by reducing cholesterol production in the liver 1. Other medications include ezetimibe (10mg daily), which decreases intestinal cholesterol absorption; bile acid sequestrants like cholestyramine; PCSK9 inhibitors for severe cases; and fibrates for high triglycerides. Regular monitoring through lipid panel blood tests is important to assess treatment effectiveness. Statins may cause muscle pain in some people, so it's crucial to report any side effects to the doctor. Treatment is important because high cholesterol contributes to plaque buildup in arteries, increasing the risk of heart disease and stroke. The use of omega-3 fatty acids, either through diet or supplements, may also be considered for risk reduction, particularly for patients with elevated triglycerides, as suggested by the 2012 ACCF/AHA focused update 1. However, the primary focus should be on statin therapy and achieving the recommended LDL-C goals.

From the FDA Drug Label

INDICATIONS AND USAGE EZETIMIBE Tablets is indicated (1): • In combination with a statin, or alone when additional low density lipoprotein cholesterol (LDL-C) lowering therapy is not possible, as an adjunct to diet to reduce elevated LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH) • In combination with a statin as an adjunct to diet to reduce elevated LDL-C in pediatric patients 10 years of age and older with HeFH.

In the atorvastatin calcium placebo-controlled clinical trial database of 16,066 patients (8,755 atorvastatin calcium vs 7,311 placebo; age range 10 to 93 years, 39% female, 91% White, 3% Black or African American, 2% Asian, 4% other) with a median treatment duration of 53 weeks, the most common adverse reactions in patients treated with atorvastatin calcium that led to treatment discontinuation and occurred at a rate greater than placebo were: myalgia (0.7%), diarrhea (0.5%), nausea (0. 4%), alanine aminotransferase increase (0.4%), and hepatic enzyme increase (0. 4%).

Treatment for High Cholesterol:

• Ezetimibe can be used in combination with a statin or alone to reduce elevated LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH) 2.
• Atorvastatin can be used to reduce elevated LDL-C in patients with primary hyperlipidemia, and has been shown to be effective in reducing the incidence of ischemic stroke 3.
• The choice of treatment should be based on the individual patient's needs and medical history, and should be made in consultation with a healthcare professional.
• It is essential to note that both ezetimibe and atorvastatin should be used as an adjunct to diet and lifestyle modifications to reduce cholesterol levels.

From the Research

Treatment Options for High Cholesterol

• Statins are the first-line therapy for treating dyslipidemia due to their low-density lipoprotein cholesterol (LDL-C) lowering efficacy, superior event-reduction data, and unrivaled cost-effectiveness 4.
• For patients who are intolerant of statins, other agents such as ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), and bempedoic acid can be used to lower LDL-C levels and reduce the risk of major adverse cardiovascular events (MACE) 4, 5.
• Ezetimibe lowers LDL-C by reducing intestinal absorption of cholesterol, while PCSK9i lower LDL-C by increasing the number and durability of hepatic LDL receptors 4, 5.
• Bempedoic acid reduces hepatic cholesterol synthesis and can be used in combination with ezetimibe and PCSK9i to synergistically lower LDL-C levels 4.

Non-Statins Therapies

• Ezetimibe and PCSK9i are evidence-based, non-statin therapies that can be used to lower LDL-C levels and reduce the risk of MACE in patients who are intolerant of statins or have residual cholesterol risk despite statin therapy 6, 5, 7.
• A meta-analysis of randomized trials found that PCSK9i lowered LDL-C levels significantly more than ezetimibe in patients not on statins, including those who are statin intolerant 7.
• The combination of ezetimibe and PCSK9i may be useful in the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD) in patients who are statin intolerant or not receiving statins 7.

Lifestyle Changes

• Physical activity is a critical component of first-line treatment for elevated blood pressure or cholesterol, and can be used in combination with pharmacological therapies to lower LDL-C levels and reduce the risk of MACE 8.
• The American Heart Association recommends lifestyle approaches, including physical activity, as the first line of therapy for patients with mildly or moderately elevated blood pressure and blood cholesterol 8.