Challenges

• Inadequate response in those at high-risk or those with very high low-density lipoprotein cholesterol (LDL-C) levels.
• Intolerance to available therapy or at higher doses.
• Short- and long-term side effects of therapy with the current lipid-lowering therapy (LLT).
• Interaction of LLT with concomitant medication.
• Inadequate response/benefit from current therapies for raising high-density lipoprotein (HDL).
• Inadequate response from current therapies for lowering triglyceride (TG).
• Assessing newer targets to prevent cardiovascular disease (CVD).

Newer drugs in clinical practice

• PCSK9 inhibitors
• Monoclonal antibodies - Evolocumab and alirocumab
• PCSK9 inhibitors - siRNA molecule - Inclisiran
• Bempedoic acid
• Eicosapentaenoic acid (EPA)

Angiopoietin-like protein 3 (ANGPTL3) is a key modulator of plasma lipoprotein levels. Evinacumab is a full human monoclonal antibody and inhibits ANGPTL3.

Three new drugs targeting Lp(a) are in development; all siRNA-based therapies: Pelacarsen, Olpasiran and SLN360.

Obicetrapib is a selective cholesteryl ester transfer protein (CETP) inhibitor; a daily dose of 10 mg obicetrapib in combination with moderate-intensity statins for 12 weeks resulted in an incremental LDL-C reduction of up to 50% compared with statin monotherapy.