[PCSK9 Inhibitors - the magic bullet for LDL cholesterol reduction?]

Area of Science:

• Biochemistry
• Cardiovascular Medicine
• Pharmacology

Background:

• Proprotein convertase subtilisin/kexin type 9 (PCSK9) is crucial in LDL cholesterol (LDL-C) metabolism.
• Loss-of-function mutations in PCSK9 gene lead to reduced plasma LDL-C levels.
• PCSK9 promotes lysosomal degradation of LDL receptors, hindering LDL-C clearance.

Purpose of the Study:

• To evaluate the efficacy and safety of novel PCSK9 inhibitors.
• To assess the impact of PCSK9 inhibition on LDL receptor recycling and LDL-C levels.
• To review the clinical trial data for PCSK9 inhibitors like alirocumab and evolocumab.

Main Methods:

• Monoclonal antibodies targeting PCSK9 were developed.
• Clinical trials were conducted in statin-treated and statin-naïve patients.
• LDL-C levels and LDL receptor dynamics were monitored.

Main Results:

• PCSK9 inhibitors induced up to 70% reduction in LDL-C.
• Inhibitors promote LDL receptor recycling, increasing cell surface receptor density.
• Serious side effects requiring treatment cessation were rare.

Conclusions:

• PCSK9 inhibitors represent a promising new class of lipid-lowering drugs.
• Early approval by EMA highlights potential cardiovascular benefits.
• Further data on cardiovascular events and mortality are anticipated in 2017.