What is the best way to lower Low-Density Lipoprotein (LDL) cholesterol?

From the Guidelines

The best way to lower Low-Density Lipoprotein (LDL) cholesterol is through the use of statins, with a goal of reducing LDL-C to <1.4 mmol/L (<55 mg/dL) and by at least 50% if the baseline LDL-C level is 1.8-3.5 mmol/L (70-135 mg/dL).

Key Points

• Statins are the first-line therapy for lowering LDL-C, with a reduction of 35% to 55% depending on the type and dose 1.
• The goal of treatment is to lower LDL-C to <1.4 mmol/L (<55 mg/dL) and to reduce it by at least 50% if the baseline LDL-C level is 1.8-3.5 mmol/L (70-135 mg/dL) 1.
• In patients who cannot achieve the desired level of LDL-C reduction with statins alone, the addition of ezetimibe has been shown to decrease cholesterol and cardiovascular events 1.
• Lifestyle intervention, including diet, increased physical activity, weight loss, and smoking cessation, may also help to lower LDL-C levels, but statins are the most effective treatment 1.

Treatment Guidelines

• The American College of Cardiology/American Heart Association (ACC/AHA) recommends statin therapy for patients with established atherosclerotic cardiovascular disease (ASCVD) and for those with a 10-year risk for ASCVD ≥7.5% 1.
• The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) recommends LDL-lowering therapy for patients with high-risk conditions, including established CHD and CHD risk equivalents, with a goal of lowering LDL-C to <100 mg/dL 1.

Medications

• Statins: simvastatin, atorvastatin, pravastatin, etc.
• Ezetimibe: can be added to statins to further reduce LDL-C levels.
• Fibrates: can be used to lower triglycerides and raise HDL cholesterol, but are not as effective as statins in lowering LDL-C 1.

From the Research

Methods to Lower Low-Density Lipoprotein (LDL) Cholesterol

• Statins are considered the most consistently effective means of lowering LDL cholesterol, with the most potent statins, such as rosuvastatin and atorvastatin, capable of getting most patients to their LDL cholesterol goals 2
• Combinations of statins with other drugs, such as exchange resins, may be necessary for patients who require additional lipid lowering 2, 3
• Inhibition of PCSK9 protein with monoclonal antibodies can reduce LDL cholesterol by more than 60% and is effective in the prevention of cardiovascular disease, although its use is restricted due to cost 3, 4
• Dietary approaches, such as substituting saturated fatty acids with polyunsaturated fatty acids and consuming foods like nuts and brans, can lower LDL cholesterol by 10-20% 5

Goals for LDL Cholesterol Reduction

• The National Cholesterol Education Program recommends an optional goal of <70 mg/dl for patients at very high risk for coronary heart disease 2
• Recent guidelines in Europe and Japan suggest lowering LDL cholesterol levels to <70 mg/dl for high-risk patients 4
• There is no evidence that achieving and maintaining low levels of LDL cholesterol results in adverse effects, and lower levels are associated with greater cardiovascular benefit 2, 3, 6, 4

Considerations for LDL Cholesterol Reduction

• The degree of reduction in LDL cholesterol is more important in affecting risk than the means used to lower LDL 2
• On-treatment LDL cholesterol concentrations show a robust relationship with cardiovascular disease events, and lowering LDL cholesterol to very low levels is considered the best preventative strategy, particularly for those at highest risk 6
• Mendelian randomization studies and human genetics suggest that "normal" LDL cholesterol levels may be too high, and that lower levels may be optimal 4