How can I lower my low‑density lipoprotein (LDL) cholesterol?

How to Reduce LDL Cholesterol

Start with therapeutic lifestyle changes (TLC) for all patients, then add statin therapy to achieve at least a 30–40% LDL-C reduction, with treatment intensity and targets determined by cardiovascular risk stratification. 1, 2

Risk-Stratified LDL-C Targets

Your LDL-C goal depends on your cardiovascular risk category:

• Very high-risk patients (established atherosclerotic cardiovascular disease or recent acute coronary syndrome): Target LDL-C < 70 mg/dL (or < 55 mg/dL per newer international guidance) 1, 2

• High-risk patients (diabetes, multiple risk factors, or 10-year cardiovascular risk > 20%): Target LDL-C < 100 mg/dL 1, 2, 3

• Moderately high-risk patients (≥1 risk factor, 10–20% 10-year risk): Target LDL-C < 130 mg/dL, with < 100 mg/dL as an optional therapeutic goal 1, 2, 3

• Lower-risk patients: Target LDL-C < 160 mg/dL 4, 3

The principle of "lower is better for longer" and "the earlier the better" should guide LDL-C management, particularly in high-risk individuals. 2

Therapeutic Lifestyle Changes (First-Line for All Patients)

TLC must be implemented regardless of whether medications are used, as lifestyle modifications reduce LDL-C through multiple mechanisms beyond pharmacotherapy. 1, 2

Dietary Modifications

• Limit saturated fat to < 7% of total energy intake – this is the single most important dietary change for LDL-C reduction 1, 2, 4

• Eliminate trans fats (keep < 1% of total calories) 2

• Restrict dietary cholesterol to < 200 mg/day (approximately one egg yolk) 1, 2, 4

• Increase soluble (viscous) fiber to 10–25 g/day – this lowers LDL-C by 5–10% through binding bile acids and cholesterol in the intestine 1, 2, 4. Food sources include oat bran, rolled oats, whole oat flour, and whole-grain barley. 2

• Add plant sterols/stanols 2 g/day – this lowers LDL-C by an additional 10–15% 1, 2

• Consider replacing saturated fat with either carbohydrates or monounsaturated fats, though increasing total dietary fat can lead to weight gain 1

Weight Management and Physical Activity

• Achieve 5–10% weight loss if overweight or obese – this improves all lipid parameters and reduces visceral adiposity 2

• Perform ≥150 minutes/week of aerobic exercise – this reduces triglycerides, modestly raises HDL-C, and improves insulin sensitivity 1, 2, 4

Monitoring Lifestyle Changes

• Reassess LDL-C 6 weeks after initiating dietary changes to determine if pharmacotherapy is needed 2

• Continue TLC even after starting medications, as the benefits are additive 1, 2

Pharmacologic Therapy

When to Initiate Statin Therapy

Statins are the cornerstone of LDL-C-lowering pharmacotherapy and the only drug class with consistent reductions in cardiovascular mortality. 5

• High-risk patients: Initiate statin if LDL-C ≥ 100 mg/dL after TLC 1, 3

• Moderately high-risk patients: Initiate statin if LDL-C ≥ 130 mg/dL after TLC; consider starting if LDL-C 100–129 mg/dL 1, 3

• Lower-risk patients: Initiate statin if LDL-C ≥ 160 mg/dL after TLC 3

Statin Intensity and Selection

Drug therapy should achieve at least a 30–40% reduction in LDL-C levels. 1, 2

• High-intensity statins (atorvastatin 40–80 mg or rosuvastatin 20–40 mg) for very high-risk and high-risk patients 2, 4

• Moderate-intensity statins (atorvastatin 10–20 mg, rosuvastatin 5–10 mg, simvastatin 20–40 mg) for moderately high-risk patients 4, 3

• Rosuvastatin produces significantly greater LDL-C reductions than other statins at equivalent doses 6

• Monitor for myopathy (unexplained muscle pain, tenderness, weakness), especially with high-dose therapy or drug interactions 7

• Check liver enzymes and monitor for hepatic dysfunction (fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice) 7

Non-Statin Add-On Therapies (When Statins Alone Are Insufficient)

If LDL-C goals are not achieved on maximally tolerated statin therapy:

Second-line: Ezetimibe

• Add ezetimibe 10 mg daily to statin therapy – this provides an additional 15–25% LDL-C reduction 2, 8

Third-line: PCSK9 Inhibitors

• PCSK9 inhibitors (alirocumab, evolocumab) are recommended for very high-risk patients who do not reach LDL-C < 55 mg/dL despite maximally tolerated statin plus ezetimibe 2, 9

• Alirocumab is FDA-approved to reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease 9

• Dosing for alirocumab: 75 mg every 2 weeks or 300 mg every 4 weeks subcutaneously; may increase to 150 mg every 2 weeks if LDL-C response is inadequate 9

• Inclisiran (a long-acting PCSK9 modulator administered subcutaneously every 6 months) offers adherence advantages 2, 8

Alternative: Bempedoic Acid

• Bempedoic acid 180 mg daily is an alternative for patients intolerant to statins – it acts on the same metabolic pathway as statins but is specifically activated in the liver, not skeletal muscle, reducing myopathy risk 2, 8

Up-front combination therapy (statin + ezetimibe ± PCSK9 inhibitor) should be considered for extremely high-risk individuals to improve adherence and effectiveness. 2

Additional Agents for Specific Lipid Abnormalities

• Fibrates or niacin may be considered for high-risk patients with elevated triglycerides (> 200 mg/dL) or low HDL-C despite LDL-C control 1, 4, 3

• Omega-3 fatty acids (fish oils) can be used for persistently elevated triglycerides, though they may increase LDL-C and require monitoring 1

• In severe hypertriglyceridemia (> 1,000 mg/dL), restrict all dietary fats and start lipid-lowering medication promptly to prevent pancreatitis 1, 2

Monitoring and Follow-Up

• Reassess LDL-C 4–6 weeks after initiating or adjusting therapy to evaluate response 2, 4, 9

• For patients on alirocumab 300 mg every 4 weeks, measure LDL-C just prior to the next scheduled dose, as LDL-C can vary between doses 9

• Monitor lipid panels every 4–6 months until LDL-C goal is achieved, then every 6–12 months 2, 4

• Monitor medication adherence, as approximately 70% of patients fail to achieve lipid goals in routine practice due to insufficient treatment intensity or poor adherence 2

Critical Pitfalls and Caveats

• Do not rely on the HDL/LDL ratio – it is an obsolete measure; focus on absolute LDL-C levels 10

• Patients with diabetes are automatically classified as high-risk and derive substantial benefit from LDL-C-lowering therapy 1, 2

• Statin therapy may increase HbA1c and fasting glucose – optimize lifestyle measures including regular exercise, healthy body weight, and healthy food choices 7

• When taking rosuvastatin with aluminum and magnesium hydroxide antacids, administer rosuvastatin at least 2 hours before the antacid 7

• Soluble fiber supplementation is safe and effective but has not been shown to reduce cardiovascular events; it should be viewed as an adjunct rather than a replacement for proven pharmacologic therapies 2

• Combination therapy with non-statin agents (other than ezetimibe and PCSK9 inhibitors) has not consistently shown improved clinical outcomes and carries increased risk of adverse events 5

• Aggressive LDL-C lowering early in atherosclerosis can dramatically regress plaque and potentially "reset the vascular aging clock" 1