Introduction to Lipfendra (Enlicitide)

Lipfendra is a newly approved pill by the US Food and Drug Administration (FDA) for lowering LDL (low-density lipoprotein) or "bad" cholesterol. It is a PCSK9 inhibitor, offering an alternative to statins, particularly for patients who do not achieve their target LDL levels with existing treatments.

Mechanism of Action

• Lipfendra works by inhibiting the PCSK9 protein, which normally destroys LDL receptors.
• Increased LDL receptors on the liver allow for more effective removal of LDL cholesterol from the bloodstream, reducing LDL levels by 50-60%.

Target Patients

• Patients at high cardiovascular risk, especially those with a history of heart attacks, angioplasty, or established coronary artery disease (CAD).
• Those with heterozygous familial hypercholesterolaemia (HeFH) and very high cholesterol levels despite standard treatment.

Comparison with Statins and Injectables

• Statins remain the first-line treatment due to cost-effectiveness and proven efficacy.
• PCSK9 inhibitors, previously only available as injectables, are reserved for high-risk patients or those intolerant to statins.
• Lipfendra presents a convenient oral alternative, although it may be expensive.

Efficacy and Ongoing Research

A cardiovascular outcomes trial is underway to confirm Lipfendra’s effectiveness in reducing heart attacks and strokes, complementing its LDL-lowering capabilities.

ApoB Reduction

• Lipfendra also lowers apolipoprotein B (ApoB) by about 50%, which is significant as ApoB reflects the number of cholesterol-carrying particles, not just total cholesterol.
• Particularly important for patients with diabetes and dyslipidaemia, as they may have a high number of harmful small, dense LDL particles despite normal LDL levels.

Cholesterol Screening Recommendations

• Adults should check cholesterol levels at least once between ages 18 and 29 to detect inherited disorders.
• Regular screening every five years is advised for those with normal levels and low risk, with more frequent checks recommended for individuals with risk factors like diabetes, hypertension, or family history of heart disease.