Oral Cholesterol Medication Shows Promise as Alternative to Injectable Therapies

For individuals who have experienced heart attacks or strokes, or who face high cardiovascular risk, a new daily oral medication may provide an effective alternative to injectable cholesterol-lowering therapies. Research presented at the American Heart Association's Scientific Sessions 2025 indicates that the investigational drug enlicitide reduced LDL cholesterol by up to 60%, matching the effectiveness of injectable PCSK9 inhibitors while offering greater convenience for patients.

The study, known as the CORALreef Lipids trial, enrolled 2,912 adults with an average age of 63 years, 39% of whom were women. All participants had experienced previous cardiovascular events or were assessed as having intermediate to high risk for future heart attacks or strokes. Despite being on stable lipid-lowering therapy, including statins for 97% of participants, their LDL levels remained above recommended targets. Lead study author Ann Marie Navar, M.D., Ph.D., explained that many patients struggle to reach guideline-recommended cholesterol targets with current therapies, leaving them at unnecessary risk of cardiovascular events.

After 24 weeks of daily treatment with 20 mg of enlicitide, participants showed significant improvements across multiple cholesterol markers. Beyond the 60% reduction in LDL cholesterol, the medication also produced a 53% reduction in non-HDL cholesterol, a 50% reduction in ApoB protein, and a 28% reduction in Lp(a) lipoprotein. The safety profile appeared comparable to placebo, with 10% of enlicitide users experiencing serious side effects versus 12% in the placebo group. Only 3% of participants discontinued enlicitide due to side effects compared to 4% in the placebo group.

Navar emphasized the clinical significance of these findings, noting that seven out of ten participants taking enlicitide achieved both at least a 50% reduction in LDL-C and levels below 70 mg/dL. More than two-thirds reached the more aggressive target of below 55 mg/dL with at least 50% reduction. The results with enlicitide were nearly identical to those achieved with injectable PCSK9 inhibitors alirocumab and evolocumab, and numerically better than the siRNA medication inclisiran. Additional information about the American Heart Association's scientific standards and funding transparency is available at https://www.heart.org.

The implications of this research are substantial for cardiovascular care. PCSK9 inhibitors, while effective, require injections that can be inconvenient and present barriers to adherence for some patients. An oral alternative could improve treatment accessibility and consistency. The ongoing CORALreef outcomes trial will determine whether the cholesterol reductions achieved with enlicitide translate to reduced rates of heart attacks and strokes. For high-risk patients who cannot achieve target cholesterol levels with current therapies, this oral medication could represent a significant advancement in preventive cardiovascular care.