When do you target a low-density lipoprotein (LDL) level of 1.4 mmol/L?

From the Guidelines

Targeting an LDL level of 1.4 mmol/L is recommended for patients at very high cardiovascular risk, particularly those with established atherosclerotic cardiovascular disease (ASCVD), multiple major risk factors, or those with diabetes with target organ damage, as evidenced by the most recent guidelines 1. This aggressive lipid target is typically pursued using high-intensity statin therapy such as atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily.

• The aim is to reduce LDL-C by >50% from baseline and to achieve LDL-C <1.4 mmol/L (<55 mg/dL) 1.
• If statins alone are insufficient to reach this target, combination therapy may be necessary, adding ezetimibe 10 mg daily as a second-line agent 1.
• For patients still not at goal, PCSK9 inhibitors like evolocumab (140 mg every 2 weeks) or alirocumab (75-150 mg every 2 weeks) may be added 1. This intensive LDL-lowering approach is based on evidence that lower LDL levels correlate with reduced cardiovascular events in high-risk populations, with clinical trials demonstrating that "lower is better" for these patients 1. Regular monitoring of lipid levels every 3-6 months is important to assess treatment efficacy, along with liver function tests and assessment for muscle symptoms to monitor for potential statin side effects. The recommendation to target an LDL level of 1.4 mmol/L is supported by the 2024 guidelines for cardiovascular disease and risk management in diabetes, which emphasize the importance of achieving this target in patients at very high cardiovascular risk 1.

From the Research

Targeting LDL 1.4 mmol/L

• The decision to target a low-density lipoprotein (LDL) level of 1.4 mmol/L depends on various factors, including the patient's cardiovascular risk and medical history 2.
• Studies have shown that achieving LDL cholesterol target levels <1.81 mmol/L may provide extra cardiovascular protection in patients at high risk 2.
• However, the benefits of intensive statin therapy in reducing cardiovascular events have been debated, with some studies suggesting that targeting LDL cholesterol levels <1.81 mmol/L may not be necessary for all patients 3.
• The 2019 study published in Diabetes, Obesity & Metabolism found that achieving LDL cholesterol target levels <1.81 mmol/L was associated with a lower incidence of cardiovascular events in patients with type 2 diabetes and hyperlipidaemia 2.
• In contrast, a 2021 review published in BMJ Evidence-Based Medicine suggested that recommending cholesterol-lowering treatment based on estimated cardiovascular risk may not be effective in identifying high-risk patients and may lead to unnecessary treatment of low-risk individuals 3.

Patient-Specific Factors

• Patient-specific factors, such as age, sex, and medical history, can influence the decision to target an LDL level of 1.4 mmol/L 4.
• For example, a study published in Cardiovascular Diabetology found that female sex, younger age, higher HDL-c, and elevated triglycerides were associated with delayed prescription of statin treatments in patients with and without diabetes 4.
• The choice of statin and dosage can also impact the achievement of LDL targets, with some studies suggesting that rosuvastatin may be more effective than other statins in reducing LDL cholesterol levels 5, 6.

Clinical Guidelines

• Clinical guidelines for LDL targets vary depending on the patient population and cardiovascular risk 2, 3.
• The National Cholesterol Education Program Adult Treatment Panel III recommends LDL targets based on cardiovascular risk, with more aggressive targets for patients at higher risk 5, 6.
• However, the optimal LDL target for individual patients remains a topic of debate, and further research is needed to determine the most effective and safe approach to LDL management 3.