From the Guidelines
To reduce cholesterol, a combination of lifestyle modifications and medications, prioritizing statins as first-line therapy, is recommended. This approach is based on the most recent evidence from the 2024 International Lipid Expert Panel (ILEP) recommendations 1, which emphasize the importance of upfront lipid-lowering combination therapy in patients with established atherosclerotic cardiovascular disease and those at very high risk of recurrent events.
Lifestyle Modifications
Key lifestyle modifications include:
- Dietary changes: reducing saturated fats, trans fats, and cholesterol intake while increasing soluble fiber (oats, beans, fruits) and plant sterols 1
- Exercise: aiming for 30-60 minutes of moderate exercise most days of the week 1
- Weight loss: achieving a 5-10% weight loss if overweight, as this can significantly improve cholesterol levels
- Limiting alcohol consumption and quitting smoking
Medications
For medications, the choice depends on cholesterol levels, cardiovascular risk, and individual factors. Statins are the first-line therapy, including atorvastatin (10-80mg daily), rosuvastatin (5-40mg daily), simvastatin (10-40mg daily), or pravastatin (10-80mg daily) 1. These work by inhibiting cholesterol production in the liver. Other options include:
- Ezetimibe (10mg daily), which blocks intestinal cholesterol absorption
- Bile acid sequestrants like cholestyramine
- PCSK9 inhibitors (evolocumab, alirocumab) for severe cases
- Fibrates (fenofibrate, gemfibrozil) primarily for high triglycerides
Monitoring and Adjustment
Regular monitoring with lipid panels every 3-12 months is essential to assess treatment effectiveness and adjust therapy as needed 1. This approach ensures that the chosen interventions work together to reduce LDL ("bad") cholesterol while potentially raising HDL ("good") cholesterol, ultimately lowering cardiovascular disease risk. The 2024 ILEP recommendations 1 provide the most recent and highest quality guidance on the optimal use of lipid-lowering therapy, emphasizing the importance of combination therapy in high-risk patients and the role of new agents like bempedoic acid and PCSK9 inhibitors in achieving significant reductions in LDL-C levels.
From the FDA Drug Label
EZETIMIBE Tablets is indicated: 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 combination with fenofibrate as an adjunct to diet to reduce elevated LDL-C in adults with mixed hyperlipidemia In combination with a statin, and other LDL-C lowering therapies, to reduce elevated LDL-C levels in adults and in pediatric patients 10 years of age and older with homozygous familial hypercholesterolemia (HoFH) As an adjunct to diet for the reduction of elevated sitosterol and campesterol levels in adults and in pediatric patients 9 years of age and older with homozygous familial sitosterolemia
The interventions to reduce cholesterol include:
- Diet: as an adjunct to reduce elevated LDL-C
- Ezetimibe: alone or in combination with a statin, or fenofibrate, to reduce elevated LDL-C
- Statin: in combination with ezetimibe to reduce elevated LDL-C
- Fenofibrate: in combination with ezetimibe to reduce elevated LDL-C in adults with mixed hyperlipidemia
- Other LDL-C lowering therapies: in combination with ezetimibe and a statin to reduce elevated LDL-C levels in adults and pediatric patients with homozygous familial hypercholesterolemia (HoFH) 2 2 2
From the Research
Interventions to Reduce Cholesterol
- There are several interventions that can be used to reduce cholesterol levels, including:
- Statins: These are a type of medication that can help lower LDL (bad) cholesterol levels 3, 4
- Ezetimibe: This is a medication that can help reduce the absorption of cholesterol from the intestine, and can be used in combination with statins to further lower LDL cholesterol levels 3, 5, 6, 7
- PCSK9 inhibitors: These are a type of medication that can help lower LDL cholesterol levels by inhibiting the action of the PCSK9 protein, which can help remove LDL receptors from the liver 3, 4, 6, 7
- The effectiveness of these interventions can vary depending on the individual and their specific health needs, but studies have shown that they can be effective in reducing LDL cholesterol levels and improving cardiovascular outcomes 5, 6, 7
- The choice of intervention will depend on a variety of factors, including the individual's baseline LDL cholesterol level, their overall health status, and their risk of cardiovascular disease 6, 7
- It's worth noting that the percentage LDL-C reduction with statins, ezetimibe, and PCSK9 inhibition is not attenuated in patients starting with lower baseline LDL-C levels, and is even greater for PCSK9 inhibition 7
Combination Therapy
- Combination therapy with statins and ezetimibe or PCSK9 inhibitors can be effective in further lowering LDL cholesterol levels and improving cardiovascular outcomes 3, 5, 6
- The addition of ezetimibe to statin therapy has been shown to reduce the risk of major cardiovascular events, including myocardial infarction and stroke 5
- The addition of PCSK9 inhibitors to statin therapy has also been shown to reduce the risk of major cardiovascular events, including myocardial infarction and stroke 4, 6
Patient-Specific Factors
- The effectiveness of these interventions can vary depending on patient-specific factors, such as baseline LDL cholesterol level, overall health status, and risk of cardiovascular disease 6, 7
- Patients with very high cardiovascular risk may benefit from more intensive LDL-C lowering therapy, including the use of PCSK9 inhibitors 6
- Patients with lower baseline LDL cholesterol levels may still benefit from intensive LDL-C lowering therapy, including the use of PCSK9 inhibitors 7