LDL cholesterol: How low to go?

Area of Science:

• Cardiology
• Lipid Metabolism
• Preventive Medicine

Background:

• The causal link between LDL cholesterol and atherosclerotic cardiovascular disease (ASCVD) is well-established, extending to very low levels.
• Current guidelines face challenges in setting LDL cholesterol targets due to the continuous risk association.

Purpose of the Study:

• To address the clinical dilemma of LDL cholesterol lowering in the era of potent therapies.
• To guide the selective use of advanced lipid-lowering treatments based on risk stratification.

Main Methods:

• Review of epidemiological data and large-scale outcome trials.
• Analysis of the implications of potent LDL-lowering agents, such as PCSK9 inhibitors.
• Application of risk-benefit principles for combination lipid-lowering therapy.

Main Results:

• Evidence supports a continuous, causal relationship between LDL cholesterol and ASCVD risk, without a 'safe' lower threshold.
• Proprotein convertase/subtilisin kexin type 9 (PCSK9) inhibitors enable profound LDL cholesterol reduction.
• Health economic considerations necessitate selective application of these advanced therapies.

Conclusions:

• There is no scientific basis for an LDL cholesterol 'floor' or target.
• Prioritizing patients with established cardiovascular disease (CVD) and elevated LDL cholesterol on statins maximizes absolute risk reduction.
• Selective use of potent lipid-lowering therapies, guided by risk, is essential for optimizing outcomes and resource allocation.