Cholesterol tablet cut LDL levels by 57%

A once-daily cholesterol tablet lowered LDL, or “bad” cholesterol, by an average of 57.1% over 24 weeks in a large clinical trial of adults at risk of heart disease.

The drug, enlicitide, works by blocking a protein known as PCSK9. That gives it an oral route to target the same pathway used by injectable cholesterol-lowering medicines. LDL is commonly described as bad cholesterol because high levels can contribute to fatty buildup in the arteries.

In the study, enlicitide was tested against a placebo, which had no active ingredient. LDL levels increased by 3% in the placebo group, producing an adjusted difference of 55.8 percentage points between the two groups.

The findings, published in The New England Journal of Medicine, involved nearly 2,900 adults who had either already experienced a major atherosclerotic heart or vascular event or were considered at risk for a first one. Many participants were already taking statins or other cholesterol-lowering medicines.

Atherosclerosis develops when fatty deposits accumulate in artery walls. Those deposits can raise the risk of heart attacks and strokes, making LDL reduction an important part of cardiovascular care.

The liver clears LDL from the bloodstream using receptors on its cells. PCSK9 limits the number of those receptors, and blocking the protein helps the liver remove more LDL.

At the same time, researchers are also examining blood tests that could improve how heart attack and stroke risk is assessed.

Most earlier PCSK9-targeting treatments have been injected. Enlicitide is taken by mouth, offering a different way to use the same biological pathway.

The U.S. Food and Drug Administration approved enlicitide, sold as Lipfendra, for lowering LDL in adults with high cholesterol, together with diet and exercise. Availability and approval can vary by country.

The trial measured changes in cholesterol, not a 57% drop in heart attacks or strokes. Larger and longer studies are still needed to determine its direct effects on those outcomes.

Researchers also tracked side effects during the study. As with any treatment, its benefits and risks need to be weighed alongside a person’s overall health and other medicines.

Participants were randomly assigned to receive either enlicitide or placebo, and neither the participants nor the researchers knew who received which pill during the blinded phase. That approach helps make comparisons more dependable.

The study also looked at other blood markers linked to cardiovascular risk. Those changes add to understanding of the drug’s effects, but they are not the same as measuring heart attacks, strokes or survival directly.

Led by Ann Marie Navar of UT Southwestern Medical Center and funded by Merck, the research adds an oral option to the group of treatments that lower LDL through PCSK9.

Source: UT Southwestern Medical Center.