LDL Cholesterol Goal Ranges Based on Cardiovascular Risk
For patients with established atherosclerotic cardiovascular disease (ASCVD), the LDL-C goal is <55 mg/dL (<1.4 mmol/L), and for those with recurrent cardiovascular events despite optimal therapy, the target should be even lower at <40 mg/dL (<1.0 mmol/L). 1, 2
Risk-Stratified LDL-C Goals
Very High-Risk Patients: <55 mg/dL (<1.4 mmol/L)
Very high-risk status includes:
- Established ASCVD (prior myocardial infarction, stroke, peripheral arterial disease) 3
- Severe chronic kidney disease 4
- Diabetes with target organ damage 4, 3
- Familial hypercholesterolemia with ASCVD 5
For these patients, aim for at least a 50% reduction in LDL-C if baseline is between 70-135 mg/dL. 3
Extreme Risk Patients: <40 mg/dL (<1.0 mmol/L)
This newly defined category applies to patients with recurrent cardiovascular events despite maximum tolerated statin-based therapy. 2 This represents the most aggressive target for those who continue to experience events despite optimal medical management.
High-Risk Patients: <70 mg/dL (<1.8 mmol/L)
High-risk status includes:
- Multiple cardiovascular risk factors without established disease 3
- Diabetes without target organ damage 3
- Target organ damage from hypertension 4
- Moderate chronic kidney disease 3
- Familial hypercholesterolemia without ASCVD 5
Aim for at least a 30-40% reduction in LDL-C levels when initiating therapy. 4
Moderate Risk Patients: <100 mg/dL (<2.6 mmol/L)
For patients at moderate cardiovascular risk, the LDL-C target is <100 mg/dL, though <70 mg/dL represents a reasonable therapeutic option. 3, 2
Low Risk Patients: <115 mg/dL (<3.0 mmol/L)
For low-risk hypertensive patients, the LDL cholesterol target is <115 mg/dL. 4, 2
Treatment Algorithm to Achieve Goals
Step 1: Initial Therapy for Very High-Risk/ASCVD Patients
Initiate high-intensity statin therapy immediately (atorvastatin 40-80 mg or rosuvastatin 20-40 mg), or consider upfront combination therapy with statin plus ezetimibe if baseline LDL-C is very high. 1, 3
Special consideration for patients with diabetes/metabolic syndrome: Consider pitavastatin with ezetimibe or lower-dose high-intensity statin with ezetimibe to reduce new-onset diabetes risk. 1
Step 2: Reassess at 4-6 Weeks
If LDL-C remains above goal (<55 mg/dL for very high-risk), immediately add ezetimibe to the statin regimen. 1 This combination can reduce LDL-C by up to 47%. 1
Step 3: Reassess at 4-6 Weeks After Adding Ezetimibe
If LDL-C is still not at goal, add:
- PCSK9 inhibitors (alirocumab, evolocumab - subcutaneous injection every 2-4 weeks) or inclisiran (subcutaneous injection twice yearly) 1
- Alternative: Bempedoic acid, particularly beneficial for patients with diabetes or metabolic concerns 1
Critical Implementation Points
The evidence consistently demonstrates that "lower is better" for LDL-C in reducing cardiovascular morbidity and mortality, with no safety threshold identified below which further lowering becomes harmful. 3 This principle justifies the increasingly aggressive targets in recent guidelines.
Common pitfall: Most very high-risk patients fail to achieve their LDL-C goals due to suboptimal uptitration of statin doses and inadequate use of combination therapy. 6 Only 15% of very high-risk patients achieve the <70 mg/dL target in real-world practice, despite 86% being on lipid-lowering therapy. 6
Discharge communication is critical: Include specific LDL-C goals and escalation instructions in discharge letters to ensure continuity between secondary and primary care. 1 The letter should specify when and how treatment should be intensified if targets are not met within the designated timeframes.
Therapeutic lifestyle changes remain essential for all patients regardless of LDL-C level and pharmacologic therapy. 4, 3