What is the recommended low-density lipoprotein (LDL) goal for patients at high risk of cardiovascular events, is it less than 70 milligrams per deciliter (mg/dL) or less than 100 mg/dL?

LDL Cholesterol Goals for High-Risk Patients

For very high-risk patients, an LDL-C goal of <70 mg/dL is recommended, while <100 mg/dL remains the standard goal for high-risk patients. 1

LDL Goals Based on Risk Category

Very High-Risk Patients

• LDL-C goal of <70 mg/dL is recommended for patients at very high cardiovascular risk 1
• Alternatively, a reduction of at least 50% if baseline LDL-C is between 70-135 mg/dL 1
• This more aggressive goal applies to patients with:
  • Established cardiovascular disease plus multiple major risk factors (especially diabetes) 1
  • Severe and poorly controlled risk factors (especially continued smoking) 1
  • Multiple risk factors of metabolic syndrome 1
  • Acute coronary syndromes 1

High-Risk Patients

• LDL-C goal of <100 mg/dL is recommended 1
• This is considered the minimal goal of treatment for high-risk patients 1
• A reduction of at least 50% if baseline LDL-C is between 100-200 mg/dL 1

Evidence Supporting Lower LDL-C Targets

• The Heart Protection Study (HPS) and PROVE IT trial demonstrated that LDL-C of 100 mg/dL is not a threshold below which no further benefit occurs 1
• PROVE IT showed that intensive LDL-C lowering with high-dose atorvastatin (achieving median LDL-C of 62 mg/dL) reduced cardiovascular events compared to standard therapy (achieving median LDL-C of 95 mg/dL) 1
• Reducing LDL-C by 30% starting at 100 mg/dL can produce another 20-30% lowering in relative risk for coronary heart disease 1
• Intensive lowering of LDL-C to well below 100 mg/dL reduces progression of coronary atherosclerotic lesions compared to reductions to approximately 110 mg/dL 1

Treatment Approach to Achieve Goals

• Statin therapy is the first-line treatment to achieve LDL-C goals 1
• An adequate dose of statin should reduce LDL-C to <100 mg/dL AND achieve at least a 30% lowering of LDL-C 1
• For very high-risk patients, higher doses of statins or combination therapy may be needed to achieve LDL-C <70 mg/dL 2
• If treatment with statins (including higher-dose and higher-potency statins) does not achieve the goal, intensification with bile acid sequestrants or niacin is reasonable 1

Current Achievement of Goals in Clinical Practice

• Despite guideline recommendations, achievement of the more aggressive LDL-C goal (<70 mg/dL) remains suboptimal 3
• Studies show that only 15-35% of very high-risk patients achieve LDL-C levels <70 mg/dL 4, 3
• Failure to uptitrate statin dose is a major factor in not achieving target goals 3
• Patients who achieve LDL-C <70 mg/dL have significantly better cardiovascular outcomes (HR=0.34,95% CI 0.17-0.70) 3

Safety Considerations

• Despite previous concerns about very low LDL-C levels, clinical trials with statin therapy have not identified significant side effects from LDL lowering per se 1
• The decision to achieve very low LDL levels should be based on evidence of benefit and recognition that there appears to be only a remote possibility of side effects 1
• For patients who do not tolerate statins, LDL-C-lowering therapy with bile acid sequestrants and/or niacin is reasonable 1

Special Considerations

• For patients with triglycerides ≥200 mg/dL, non-HDL-C should be <130 mg/dL for high-risk patients and <100 mg/dL for very high-risk patients 1
• Women and younger men are less likely to achieve their lipid goals and may require more aggressive therapy 4
• Combination lipid-lowering therapy is used infrequently in practice but may be necessary to achieve aggressive goals 4