[PERSONALIZED APPROACH TO LIPID-LOWERING THERAPY].

Area of Science:

• Cardiovascular Medicine
• Pharmacogenomics
• Lipidology

Background:

• Dyslipidemias are traditionally managed via phenotypic approaches, guiding drug selection (statins, fibrates) and setting therapeutic goals like LDL cholesterol targets.
• Genetic factors significantly influence dyslipidemias, exemplified by familial hypercholesterolemia (heterozygous and homozygous forms).
• Substantial inter-individual variability exists in response to lipid-lowering therapies, particularly statins, highlighting the need for pharmacogenetic insights.

Purpose of the Study:

• To explore the genetic underpinnings of dyslipidemias and their impact on therapeutic response.
• To introduce novel therapeutic strategies targeting PCSK9 for managing dyslipidemias, including familial hypercholesterolemia.
• To evaluate the efficacy of PCSK9 inhibitors in reducing LDL cholesterol and residual cardiovascular risk.

Main Methods:

• Phenotypic analysis of lipid profiles and clinical risk assessment for guiding therapy.
• Investigation of genetic mutations, specifically in the PCSK9 gene, associated with dyslipidemias.
• Development and clinical testing of monoclonal antibodies targeting PCSK9.
• Prospective controlled trials assessing PCSK9 inhibitors in combination with statins.

Main Results:

• Discovery of PCSK9 gene mutations has advanced understanding of familial hypercholesterolemia.
• PCSK9 inhibitors, when combined with statins, achieve significant reductions in LDL cholesterol levels.
• Ongoing trials aim to confirm the reduction of residual cardiovascular risk in patients treated with statins and PCSK9 inhibitors.

Conclusions:

• PCSK9 inhibition represents a promising therapeutic avenue for dyslipidemias, particularly severe forms like familial hypercholesterolemia.
• This approach addresses inter-individual variability in statin response and offers a strategy to further lower LDL cholesterol.
• Further research and clinical trials are crucial to establish the long-term cardiovascular benefits of PCSK9 inhibitors.