There are those who would like zero LDL cholesterol.

Area of Science:

• Cardiovascular Medicine
• Lipidology
• Pharmacology

Background:

• Established link between reduced LDL cholesterol (LDLc) and decreased cardiovascular (CV) risk.
• Progressive lowering of therapeutic LDLc targets in CV disease management and primary prevention.
• Emergence of PCSK9 inhibitors enabling LDLc reductions beyond current guideline targets.

Purpose of the Study:

• To review scientific evidence on the 'lower the better' paradigm for LDLc reduction.
• To investigate the potential for further CV risk reduction with extremely low LDLc levels.
• To assess the safety of polypharmacotherapies used for extreme LDLc reduction.

Main Methods:

• Comprehensive literature review of studies on LDLc reduction and cardiovascular outcomes.
• Analysis of data from clinical trials involving PCSK9 inhibitors and other lipid-lowering therapies.
• Evaluation of safety profiles associated with intensive LDLc-lowering strategies.

Main Results:

• Evidence supports continued LDLc reduction correlating with decreased CV risk.
• PCSK9 inhibitors facilitate unprecedented LDLc level reductions.
• Safety data on extreme LDLc lowering requires ongoing evaluation, particularly with polytherapy.

Conclusions:

• The 'lower the better' approach for LDLc is supported by current evidence.
• Achieving near-zero LDLc levels may offer further CV risk reduction.
• Careful monitoring for safety is essential when using multiple therapies for extreme LDLc lowering.