Cholesterol: new oral treatment reduces LDL more than standard statins in trial

A global trial published in the New England Journal of Medicine found the oral PCSK9 inhibitor enlicitide lowered LDL cholesterol by more than 57% at 24 weeks versus about 3% with placebo in patients already taking statins.

Researchers report an oral drug that blocks the PCSK9 protein produced large reductions in harmful LDL cholesterol in a global clinical trial. The medicine, developed from long-term work at UT Southwestern, acts independently of the liver receptor pathway that has guided cholesterol treatment for decades. The result is an oral PCSK9 inhibitor, a mechanism previously available only as injections or infusions. The trial tested the drug in patients who remained above guideline LDL targets despite standard therapy. Key facts: - The CORALreef Lipids trial was published in the New England Journal of Medicine and included more than 2,900 adults with established cardiovascular disease or high risk. - The study was double-blind and randomized; 1,935 participants received a 20 mg daily dose of enlicitide and 969 received a placebo, with primary LDL measurements at 24 weeks and follow-up through 52 weeks. - At 24 weeks, LDL cholesterol fell by more than 57% in the enlicitide group versus about a 3% change in the placebo group. - Other lipid measures, including non-HDL cholesterol, particle number, and lipoprotein(a), also declined more with enlicitide than with placebo. - Reported rates of common statin-associated side effects such as muscle pain, liver enzyme changes, and new type 2 diabetes were not higher among those taking enlicitide. - A separate clinical outcomes trial is already underway to evaluate whether the LDL reductions translate into fewer heart attacks and strokes. Summary: The trial shows an oral PCSK9 inhibitor produced large LDL reductions in people already taking statins. The researchers reported the drug works independently of LDL receptor activity, which could be relevant for patients with receptor-related genetic high cholesterol. A separate outcomes trial is underway to determine whether these lipid changes reduce heart attacks and strokes.