Oral PCSK9 Inhibitor Enlicitide Versus Oral Nonstatin Therapies: A Phase 3 Randomized Clinical Trial

Catapano AL, Mikhailova E, Navar AM, Banka P, Corral P, Saxena M, Steg PG, Verma S, Kordahi AY, Mendizabal G, Zhu P, Ballantyne CM, CORALreef AddOn Investigators

Journal of the American College of Cardiology · 10 citas

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Financiado por la industria

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Cómo se estudió

Diseño: Ensayo controlado aleatorizado (indexado por PubMed)
Estudiado en: Personas
Resultado principal: Marcadores de salud y funcionamiento

Quién lo pagó

Financiación: Financiado por la industria
Empresa: Amgen
Empresa: AstraZeneca
Empresa: Merck
Gobierno: Ministero della Salute
Empresa: Novo Nordisk
Universidad u hospital: Istituto di Ricovero e Cura a Carattere Scientifico
Empresa: Merck & Co Inc

Según 7 financiadores declarados.

Publicación

Publicado: 2026-03-30 · J Am Coll Cardiol · vol. 88 · número 3 · págs. 340–352
Editorial: Elsevier BV
Citado: 16 citas · más que el 100% de estudios similares · 100.4× el promedio de su campo
Impacto: Entre el 10 % más citado de su campo
Referencias: 33 trabajos
Acceso: Acceso abierto (revista híbrida) · CC-BY-NC-ND
Áreas de investigación: Lipoproteins and Cardiovascular Health · Cholesterol and Lipid Metabolism · Lipid metabolism and disorders
Palabras clave: PCSK9 inhibitors, LDL cholesterol lowering, bempedoic acid, ezetimibe, non-statin lipid-lowering therapy, apolipoprotein B, non-HDL cholesterol, atherosclerotic cardiovascular disease, statin-treated patients, LDL-C goal attainment, drug safety, adverse events, combination therapy, hypercholesterolemia
MeSH: humans, dicarboxylic acids, fatty acids, anticholesteremic agents, hydroxymethylglutaryl-coa reductase inhibitors, treatment outcome, administration, oral, double-blind method, aged, middle aged, female, male, cholesterol, ldl, proprotein convertase 9, pcsk9 inhibitors

DOI ↗OpenAlex ↗

51 autores

Alberico Luigi Catapano🇮🇹 · autor de correspondenciaUniversity of Milan; MultiMedica
Elina Mikhailova🇬🇧MSD (UK) Limited (United Kingdom)
Ann Marie Návar🇺🇸The University of Texas Southwestern Medical Center
Puja Banka🇺🇸Merck & Co., Inc., Rahway, NJ, USA (United States)
Pablo Corral🇦🇷Universidad Fraternidad de Agrupaciones Santo Tomás de Aquino
Manish Saxena🇬🇧Queen Mary University of London
Philippe Gabríel Steg🇫🇷Inserm; Université Paris Cité; Assistance Publique – Hôpitaux de Paris
Subodh Verma🇨🇦St. Michael's Hospital; University of Toronto
Andrew Kordahi🇺🇸Merck & Co., Inc., Rahway, NJ, USA (United States)
Geraldine Mendizabal
Pengfei Zhu🇨🇳MSD (China) Investment Co., Ltd. (China)
Christie Mitchell Ballantyne🇺🇸 · autor de correspondenciaBaylor College of Medicine
Chau-Chung Wu
Chii‐Min Hwu
Kai‐Chien Yang
Ping-Yen Liu
Kuo-Chun Hung
Sybil Charrière
Bertrand Cariou
Philippe Gabríel Steg
François Roubille
Oren Caspi
Gil Moravsky
Victor Vishlitzky
Amos Katz
Carlos Brotons Cuixart
Francisco Jose Tinahones Madueno
Nuria Rial Lorenzo
María Urquizu-Padilla
Alex Vila Belmonte
Alfonso Soto González
Devaki R. Nair
Manish Saxena🇬🇧Queen Mary University of London
Umasuthan Srirangalingam
Cesar Javier Zaidman
Ezequiel Hector Vottero
Pablo Corral🇦🇷Universidad Fraternidad de Agrupaciones Santo Tomás de Aquino
Harold Edward Bays
Frances E. Broyles
SHERYL M. MARKS
Shishir Kumar Khetan
Paul Gerard Matherne
Amit G. Shah
Ronald Stumbris
Jeffrey D. Wayne
Jean-francois Naud
A. Shekhar Pandey
Jean‐Claude Tardif
Subodh Verma🇨🇦St. Michael's Hospital; University of Toronto
John Vyselaar
Christie Mitchell Ballantyne🇺🇸 · autor de correspondenciaBaylor College of Medicine

Resumen

El texto original del estudio, en el idioma en que se publicó.

Background

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.

Objectives

This study assessed the efficacy of enlicitide, a novel oral PCSK9 inhibitor, vs other oral nonstatin therapies.

Methods

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.

Results

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.

Conclusions

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).

Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY-NC-ND).

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