Oral PCSK9 Inhibitor Enlicitide Versus Oral Nonstatin Therapies: A Phase 3 Randomized Clinical Trial.
L, C.A., Elina, M., Marie, N.A., Puja, B., Pablo, C., Manish, S., Gabriel, S.P., Subodh, V., Yacoub, K.A., Geraldine, M., Pengfei, Z., & M, B.C. (2026). Oral PCSK9 Inhibitor Enlicitide Versus Oral Nonstatin Therapies: A Phase 3 Randomized Clinical Trial.. J Am Coll Cardiol. https://doi.org/10.1016/j.jacc.2026.03.036
L CA, Elina M, Marie NA, Puja B, Pablo C, Manish S, et al. Oral PCSK9 Inhibitor Enlicitide Versus Oral Nonstatin Therapies: A Phase 3 Randomized Clinical Trial.. J Am Coll Cardiol. 2026; doi: 10.1016/j.jacc.2026.03.036
L CA, Elina M, Marie NA, et al. Oral PCSK9 Inhibitor Enlicitide Versus Oral Nonstatin Therapies: A Phase 3 Randomized Clinical Trial.[J]. J Am Coll Cardiol. 2026. DOI: 10.1016/j.jacc.2026.03.036.
@article{l2026,
author = {Catapano Alberico L and Mikhailova Elina and Navar Ann Marie and Banka Puja and Corral Pablo and Saxena Manish and Steg P Gabriel and Verma Subodh and Kordahi Andrew Yacoub and Mendizabal Geraldine and Zhu Pengfei and Ballantyne Christie M},
title = {Oral PCSK9 Inhibitor Enlicitide Versus Oral Nonstatin Therapies: A Phase 3 Randomized Clinical Trial.},
journal = {J Am Coll Cardiol},
year = {2026},
doi = {10.1016/j.jacc.2026.03.036},
note = {PMID: 42017875},
}
TY - JOUR AU - Catapano Alberico L AU - Mikhailova Elina AU - Navar Ann Marie AU - Banka Puja AU - Corral Pablo AU - Saxena Manish AU - Steg P Gabriel AU - Verma Subodh AU - Kordahi Andrew Yacoub AU - Mendizabal Geraldine AU - Zhu Pengfei AU - Ballantyne Christie M TI - Oral PCSK9 Inhibitor Enlicitide Versus Oral Nonstatin Therapies: A Phase 3 Randomized Clinical Trial. T2 - J Am Coll Cardiol PY - 2026 DO - 10.1016/j.jacc.2026.03.036 AN - PMID:42017875 ER -
Many adults fail to achieve guideline-directed low-density lipoprotein cholesterol (LDL-C) goals on statin monotherapy, requiring additional nonstatin lipid-lowering medication. Enlicitide, an oral proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor, lowered LDL-C by 60% compared with placebo; its efficacy compared with other oral nonstatin therapies has yet to be examined. This study assessed the efficacy of enlicitide, a novel oral PCSK9 inhibitor, vs other oral nonstatin therapies. In this phase 3, randomized, double-blind, active-comparator trial, statin-treated adults aged ≥18 years with LDL-C ≥55 mg/dL and a previous major atherosclerotic cardiovascular disease (ASCVD) event, or LDL-C ≥70 mg/dL if at intermediate to high risk for a first event, were randomized in 2:1:1:2 fashion to 20 mg enlicitide (n = 101), 180 mg bempedoic acid (n = 50), 10 mg ezetimibe (n = 50), or 180 mg bempedoic acid plus 10 mg ezetimibe (n = 100) once daily for 56 days. The primary endpoint was mean percentage change in LDL-C from baseline to day 56; secondary endpoints included mean percentage changes in apolipoprotein B (ApoB) and non-high-density lipoprotein cholesterol (nonHDL-C). Safety endpoints included overall adverse events (AEs) and discontinuations due to AEs. Among 301 randomized participants (mean age 64.4 years, 37% female, 98% receiving moderate- to high-intensity statin), 298 (99.0%) completed the trial. The mean percentage change in LDL-C from baseline to day 56 was -64.6% (95% CI: -68.3% to -60.9%) with enlicitide, -6.3% (95% CI: -13.5% to 0.8%) with bempedoic acid, -27.8% (95% CI: -32.3% to -23.4%) with ezetimibe, and -36.5% (95% CI: -40.8% to -32.2%) with bempedoic acid plus ezetimibe; enlicitide was superior to each comparator (all P < 0.001). Reductions in ApoB and nonHDL-C were also greater with enlicitide (all P < 0.001). Proportions of participants with AEs and discontinuations due to AEs were similar across treatment arms. In statin-treated adults with a history of a major ASCVD event or at increased risk for a first event, enlicitide achieved greater reductions in LDL-C, ApoB, and nonHDL-C than other oral nonstatin therapies, demonstrating its potential role as an important add-on option when LDL-C goals are not met with the use of statins alone. (A Study to Evaluate the Efficacy and Safety of Enlicitide Decanoate [MK-0616, Oral PCSK9 Inhibitor] Compared With Ezetimibe or Bempedoic Acid or Ezetimibe and Bempedoic Acid in Adults With Hypercholesterolemia [MK-0616-018] [CORALreef AddOn; NCT06450366).