A preliminary late-breaking study presented at the American Heart Association's Scientific Sessions 2025 suggests that a daily oral medication, enlicitide, may lower low-density lipoprotein (LDL) cholesterol as effectively as injectable PCSK9 inhibitors. The phase 3 CORALreef Lipids trial found that enlicitide reduced LDL cholesterol by up to 60% in adults with previous heart attack or stroke, or those at high risk, offering a more convenient option for patients who struggle with injections.
“This oral medication is set to be another powerful addition to the treatments we currently have to lower LDL cholesterol and hopefully prevent cardiovascular events,” said lead study author Ann Marie Navar, M.D., Ph.D., FAHA, an associate professor of cardiology at the University of Texas Southwestern Medical Center. “Many patients struggle to reach guideline-recommended cholesterol targets despite currently available therapies, leaving them at unnecessary risk of stroke and/or heart attack.”
The study enrolled 2,912 adults (average age 63; 39% women) with elevated LDL despite stable lipid-lowering therapy, including statins. Participants were randomized 2:1 to receive 20 mg enlicitide daily or placebo. At 24 weeks, enlicitide produced up to 60% LDL reduction, sustained at 52 weeks, along with significant reductions in non-HDL cholesterol (53%), ApoB (50%), and Lp(a) (28%). Seven out of 10 participants achieved at least 50% LDL reduction and levels below 70 mg/dL.
“Daily enlicitide resulted in almost identical changes in LDL, non-HDL and ApoB to those achieved with the injectable antibodies alirocumab and evolocumab,” Navar said. Serious side effects occurred in 10% of the enlicitide group versus 12% in the placebo group, with 3% and 4% discontinuing due to side effects, respectively.
The CORALreef outcomes trial is ongoing to determine if enlicitide reduces the risk of heart attack or stroke. The findings are considered preliminary until published in a peer-reviewed journal. More information is available at the American Heart Association website.
