From the Guidelines
The primary treatment option for hypercholesterolemia is a statin, which should be used up to the highest recommended dose or highest tolerable dose to reach the LDL-C goal, as recommended by the 2016 ESC/EAS guidelines for the management of dyslipidaemias 1.
Treatment Approach
The treatment approach for hypercholesterolemia involves a combination of lifestyle modifications and medication. Lifestyle changes include adopting a heart-healthy diet low in saturated fats and trans fats, regular exercise, weight management, quitting smoking, and limiting alcohol consumption.
- Key lifestyle modifications:
- Heart-healthy diet
- Regular exercise (at least 150 minutes of moderate activity weekly)
- Weight management
- Quitting smoking
- Limiting alcohol consumption
Medication Options
If lifestyle changes are not sufficient, medications may be necessary. The primary medication option is a statin, which includes atorvastatin (Lipitor), rosuvastatin (Crestor), and simvastatin (Zocor), typically taken once daily. Other medication options include ezetimibe (Zetia), PCSK9 inhibitors, bile acid sequestrants, and fibrates.
- Medication options:
- Statins (e.g., atorvastatin, rosuvastatin, simvastatin)
- Ezetimibe (Zetia)
- PCSK9 inhibitors
- Bile acid sequestrants
- Fibrates
LDL-C Goals
The LDL-C goals vary depending on the patient's risk category. 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. For patients at high CV risk, an LDL-C goal of < 2.6 mmol/L (100 mg/dL), or a reduction of at least 50% if the baseline LDL-C is between 2.6 and 5.1 mmol/L (100 and 200 mg/dL) is recommended 1.
Monitoring Treatment Effectiveness
Treatment effectiveness should be monitored through regular blood tests every 3-6 months initially, then annually once levels stabilize. These approaches work by either reducing cholesterol production in the liver, increasing its removal from the bloodstream, or blocking intestinal absorption, ultimately preventing the buildup of plaque in arteries that can lead to heart disease and stroke. The 2004 implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines also support the benefit of cholesterol-lowering therapy in high-risk patients and confirm the benefits of LDL-lowering therapy in these patients 1.
From the FDA Drug Label
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.
Atorvastatin calcium is used to reduce the risk of myocardial infarction, stroke, and angina, and to reduce the risk of hospitalization for congestive heart failure in patients with type 2 diabetes and history of stroke or myocardial infarction, and to reduce the risk of myocardial infarction and stroke in patients with type 2 diabetes without a history of myocardial infarction or stroke but with multiple risk factors.
The treatment options for hypercholesterolemia include:
- Ezetimibe: alone or in combination with a statin, as an adjunct to diet to reduce elevated LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH) 2
- Atorvastatin: to reduce the risk of myocardial infarction, stroke, and angina, and to reduce the risk of hospitalization for congestive heart failure in patients with type 2 diabetes and history of stroke or myocardial infarction, and to reduce the risk of myocardial infarction and stroke in patients with type 2 diabetes without a history of myocardial infarction or stroke but with multiple risk factors 3
- Combination therapy: ezetimibe in combination with a statin, or alone when additional 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) 2
From the Research
Treatment Options for Hypercholesterolemia
The treatment options for hypercholesterolemia include:
- Statins as first-line treatments to reduce low-density-lipoprotein cholesterol (LDL-C) and cardiovascular (CV) events 4, 5, 6, 7
- Second-line treatment options such as up-titration of statin dose, switching to a more potent statin, or combination therapy with ezetimibe 4, 7, 8
- Alternative treatments for patients who are unable to tolerate effective doses or any dose of statins, including ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and bempedoic acid 5
Combination Therapy
Combination therapy with ezetimibe and statins is an effective treatment choice for patients who cannot achieve target LDL-C levels with statin monotherapy 4, 7, 8
- The addition of ezetimibe to simvastatin, atorvastatin, or rosuvastatin monotherapy offers greater reduction in LDL-C among patients at high risk of CV disease compared to doubling the initial statin dose 4, 8
- Ezetimibe in combination with statins leads to additional LDL-C lowering and ASCVD risk reduction without raising significant safety concerns 7
Safety Evaluation
The safety of statin alternatives, including ezetimibe, PCSK9 inhibitors, and bempedoic acid, has been evaluated in several studies 5, 7
- These alternatives have shown an excellent safety profile and have not been associated with skeletal muscle symptoms or increased risk of new onset diabetes 5
- The injectable PCSK9 inhibitors are associated with a small increase in injection site reactions, and bempedoic acid is associated with a small increase in plasma uric acid and slightly increased frequency of episodes of gout in susceptible subjects 5