From the Guidelines
Lowering LDL cholesterol to very low levels (<30 mg/dL) is safe and associated with a significant reduction in major adverse cardiovascular events, making it a worthwhile goal for high-risk patients, as supported by recent studies 1.
Importance of LDL Lowering
The relationship between LDL cholesterol and coronary heart disease (CHD) risk is well-established, with a log-linear correlation observed in epidemiological data 1. Lowering LDL cholesterol is essential for reducing heart disease risk, and the primary recommendation is to target LDL levels below 100 mg/dL for most adults, and below 70 mg/dL for those with existing heart disease or diabetes.
Lifestyle Modifications
Lifestyle modifications, including dietary changes and regular exercise, play a crucial role in lowering LDL cholesterol. Reducing saturated fats, eliminating trans fats, increasing fiber intake, and consuming more plant sterols found in vegetables and nuts can help lower LDL levels. Regular exercise of at least 150 minutes per week of moderate activity significantly helps lower LDL, with studies showing improvements in the lipid profile following exercise 1.
Medications
For medications, statins are the first-line treatment, with options including atorvastatin (10-80mg daily), rosuvastatin (5-40mg daily), and simvastatin (10-40mg daily) 1. If statins aren't tolerated or don't achieve targets, ezetimibe (10mg daily) can be added. For very high-risk patients, PCSK9 inhibitors like evolocumab or alirocumab may be prescribed as injections every 2-4 weeks.
Safety of Very Low LDL Levels
Recent studies have shown that very low LDL levels (<30 mg/dL) are safe and associated with a significant reduction in major adverse cardiovascular events 1. The European and American Cholesterol Management guidelines have adopted a more aggressive lipid-lowering approach in high-risk patients, supporting the use of potent LDL-C-lowering medications to achieve very low LDL levels.
Key Points
- Lowering LDL cholesterol to very low levels (<30 mg/dL) is safe and associated with a significant reduction in major adverse cardiovascular events.
- Lifestyle modifications, including dietary changes and regular exercise, play a crucial role in lowering LDL cholesterol.
- Statins are the first-line treatment for lowering LDL cholesterol, with options including atorvastatin, rosuvastatin, and simvastatin.
- PCSK9 inhibitors like evolocumab or alirocumab may be prescribed as injections every 2-4 weeks for very high-risk patients.
From the FDA Drug Label
To reduce the risk of major adverse cardiovascular (CV) events (CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, or coronary revascularization) in adults with established cardiovascular disease To reduce the risk of: Myocardial infarction (MI), stroke, revascularization procedures, and angina in adults with multiple risk factors for coronary heart disease (CHD) but without clinically evident CHD As an adjunct to diet to reduce low-density lipoprotein (LDL-C) in: Adults with primary hyperlipidemia
The LDL-lowering effect of evolocumab and atorvastatin may help reduce the risk of heart disease by decreasing the levels of low-density lipoprotein cholesterol (LDL-C) in the blood.
- Evolocumab is used to reduce the risk of major adverse cardiovascular events in adults with established cardiovascular disease.
- Atorvastatin is used to reduce the risk of myocardial infarction, stroke, and revascularization procedures in adults with multiple risk factors for coronary heart disease. Both drugs are used as an adjunct to diet to reduce LDL-C in adults with primary hyperlipidemia 2 3.
From the Research
LDL Lowering and Heart Disease
- There is evidence that high LDL cholesterol levels cause atherosclerotic heart disease, and current guidelines recommend an LDL cholesterol target of 70 mg/dL for patients at high or very high risk 4.
- Epidemiologic studies have shown that very low LDL cholesterol levels (lower than 70 mg/dL) are associated with a very low risk of cardiovascular disease 4.
- Analyses of randomized clinical trials have shown a greater benefit in reducing the risk of cardiovascular disease among those with very low achieved LDL (below 40 mg/dL) 4.
- High-intensity statin therapy is associated with a higher rate of transaminase elevations, but no hepatic failure, a very small risk of myopathy, and an increased risk of developing diabetes, although the small increase in the risk of developing diabetes is much smaller than the marked lowering of cardiovascular risk 4.
Treatment Options
- Statins inhibit 3-hydroxyl-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) to reduce low-density lipoprotein (LDL) by about 20% to 45% 5.
- Ezetimibe inhibits cholesterol absorption by targeting the Niemann-Pick C1-like 1 protein (NPC1L1), which is related to cholesterol absorption in the intestines, and lowers LDL by about 18% when used alone and by an additional 25% when combined with statin therapy 5.
- Evolocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody, can reduce LDL from baseline by 53% to 56% 5.
- Combination therapy with additional LDL-C lowering drugs (e.g. ezetimibe, bile acid sequestrants or fibrates) should be considered for patients who do not reach the LDL-C target 6.
Achieving Optimal Lipid Goals
- Guidelines for lipid-lowering therapy recommend intensive low-density lipoprotein (LDL) cholesterol lowering for patients with coronary artery disease 7.
- Many high-risk patients are not achieving their LDL cholesterol goals, and many patients, despite being treated with lipid-lowering therapy, also have elevated triglycerides or low levels of high-density lipoprotein (HDL) cholesterol 7.
- Current European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidemias have further reduced low density lipoprotein-cholesterol (LDL-C) targets, and the attainment of these targets is largely suboptimal in very high-risk patients with established atherosclerotic cardiovascular disease 8.