Triple Versus Dual Lipid-Lowering Therapy in Acute Coronary Syndrome: The ES-BempedACS Randomized Clinical Trial

S Sergio Raposeiras-Roubín (Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid) E Emad Abu Assi (Povisa Hospital, Vigo, Spain (E.A.A.)) C César Jiménez Méndez (Cardiology Department, University Hospital Puerta del Mar, Cádiz, Spain (C.J.M., A.V.R., M.T.G.G., J.A.P.d.l.M.)) E Ester Mínguez de la Guía (Cardiology Department, University Hospital of Albacete, Spain (E.M.d.l.G., M.L.V., F.S.M., M.C.-P.)) J José Ángel Pérez Rivera (Cardiology Department, University Hospital of Burgos, Spain (J.Á.P.R., L.A.I., A.M.M., E.S.C., I.S.S.)) M Marta Marcos Mangas (Cardiology Department, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain (M.M.M., Á.V.H.-M., A.A.-S.)) A Ana Ayesta (Cardiology Department, University Hospital Central de Asturias, Oviedo, Spain (A.A., A.A. Andrémar, J.R.)) A Aitor Uribarri (Cardiology Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain (A.U., M.V.-B.).) P Pablo Jorge Pérez (Cardiology Department, University Hospital of Canarias, Tenerife, Spain (P.J.P., M.M.M.C.)) P Pablo José Antúnez Muinos (Cardiology Department, University Hospital Montecelo, Pontevedra, Spain (P.J.A.M., M.C.G.C.)) C Clara Bonanad Lozano (Cardiology Department, University Clinical Hospital of Valencia and INCLIVA Health Research Institute, Spain (C.B.L., D.B.)) A Anna Carrasquer (Hospital Universitari Joan XXIII, Tarragona, Spain) A Ana Viana-Tejedor (Cardiology Department, University Hospital Joan XXIII of Tarragona, Spain (A.C.)) P Pablo Domínguez Erquicia (Cardiology Department, University Hospital Álvaro Cunqueiro and Instituto de Investigación Sanitaria Galicia Sur, Vigo, Spain (S.R.R., P.D.E., A.A. Abejón, A.I.R.)) A Alberto Villar Ruiz (Cardiology Department, University Hospital Puerta del Mar, Cádiz, Spain (C.J.M., A.V.R., M.T.G.G., J.A.P.d.l.M.)) M Macarena López Vázquez (Cardiology Department, University Hospital of Albacete, Spain (E.M.d.l.G., M.L.V., F.S.M., M.C.-P.)) L Lara Aguilar Iglesias (Cardiology Department, University Hospital of Burgos, Spain (J.Á.P.R., L.A.I., A.M.M., E.S.C., I.S.S.)) A Alberto Alén Andrémar (Cardiology Department, University Hospital Álvaro Cunqueiro and Instituto de Investigación Sanitaria Galicia Sur, Vigo, Spain (S.R.R., P.D.E., A.A. Abejón, A.I.R.)) M Maria Vidal Burdeus (Cardiology Department, University Hospital Vall D’Hebron, Barcelona, Spain (A.U., M.V.B.)) M Marta Maria Martin Cabeza (Cardiology Department, University Hospital of Canarias, Tenerife, Spain (P.J.P., M.M.M.C.)) M María Cristina González Cambeiro (Cardiology Department, University Hospital Montecelo, Pontevedra, Spain (P.J.A.M., M.C.G.C.)) D Daznia Bompart (Cardiology Department, University Clinical Hospital of Valencia and INCLIVA Health Research Institute, Spain (C.B.L., D.B.)) J Juan Carlos Gómez Polo (Cardiology Department, University Clinical Hospital San Carlos, Madrid, Spain (A.V.-T., J.C.G.P.).) M Marina Teresa García García (Cardiology Department, University Hospital Puerta del Mar, Cádiz, Spain (C.J.M., A.V.R., M.T.G.G., J.A.P.d.l.M.)) A Ana Merino Merino (Cardiology Department, University Hospital of Burgos, Spain (J.Á.P.R., L.A.I., A.M.M., E.S.C., I.S.S.)) J José Rozado (Cardiology Department, University Hospital Central de Asturias, Oviedo, Spain (A.A., A.A. Andrémar, J.R.)) J José Antonio Panera de la Mano (Cardiology Department, University Hospital Puerta del Mar, Cádiz, Spain (C.J.M., A.V.R., M.T.G.G., J.A.P.d.l.M.)) F Francisco Salmerón Martínez (Cardiology Department, University Hospital of Albacete, Spain (E.M.d.l.G., M.L.V., F.S.M., M.C.-P.)) E Ester Sánchez Corral (Cardiology Department, University Hospital of Burgos, Spain (J.Á.P.R., L.A.I., A.M.M., E.S.C., I.S.S.)) I Isabel Santos Sánchez (Cardiology Department, University Hospital of Burgos, Spain (J.Á.P.R., L.A.I., A.M.M., E.S.C., I.S.S.)) Ángel Víctor Hernández-Martos (Cardiology Department, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain (M.M.M., Á.V.H.-M., A.A.-S.)) A Andrés Antelo Abejón (Cardiology Department, University Hospital Álvaro Cunqueiro and Instituto de Investigación Sanitaria Galicia Sur, Vigo, Spain (S.R.R., P.D.E., A.A. Abejón, A.I.R.)) A Andrés Iñiguez Romo (Cardiology Department, University Hospital Álvaro Cunqueiro and Instituto de Investigación Sanitaria Galicia Sur, Vigo, Spain (S.R.R., P.D.E., A.A. Abejón, A.I.R.)) M Miguel Corbi-Pascual (Cardiology Department, University Hospital of Albacete, Spain (E.M.d.l.G., M.L.V., F.S.M., M.C.-P.)) A Albert Ariza-Solé (Cardiology Department, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain (M.M.M., Á.V.H.-M., A.A.-S.))

Abstract

BACKGROUND: Current guidelines recommend a stepwise strategy to achieve low-density lipoprotein cholesterol (LDL-C) goals after acute coronary syndrome (ACS). Earlier intensive strategies based on a combination of lipid-lowering therapies (LLTs) could be useful from the onset of ACS. However, the role of bempedoic acid in ACS, particularly when combined with high-intensity statins and ezetimibe, remains uncertain. The aim of ES-BempedACS (Efficacy and Security of Bempedoic Acid in Acute Coronary Syndrome) was to compare the efficacy and safety of triple LLT (high-dose, high-intensity statin+ezetimibe+bempedoic acid) versus standard of care (high-dose, high-intensity statin+ezetimibe) after ACS. METHODS: ES-BempedACS is a multicenter, independent, pragmatic, prospective, randomized, open, blinded end point controlled trial conducted in 12 Spanish hospitals between November 2023 and October 2024. The primary end point was the proportion of patients achieving LDL-C <55 mg/dL (<1.4 mmol/L) at 8 weeks after ACS, comparing triple LLT with standard of care. RESULTS: A total of 206 patients (59.5±10.9 years of age [mean±SD]; 21.4% women) were randomized within the first 72 hours of ACS to triple LLT or standard therapy of high-intensity statin+ezetimibe (ie, dual LLT). The baseline LDL-C level was 133.6±28.8 mg/dL. After 8 weeks, the LDL-C level was reduced to <55 mg/dL in 59.4% of patients in the triple LLT group compared with 53.1% in the control group (dual LLT; P =0.376). The percentage change in LDL-C level was 57.5±17.8% and 56.9±18.5% in the triple and dual LLT groups, respectively ( P =0.823). Triple versus dual LLT showed similar results in reduction of non–high-density lipoprotein cholesterol levels (49.0±25.4 in triple LLT versus 49.1±31.2 in dual LLT; P =0.970) and triglyceride levels (14.9±36.9 in triple LLT versus 16.8±36.0 in dual LLT;) P =0.718), without differences in adverse events. CONCLUSIONS: Both dual and triple LLT after ACS allow for high rates (>50%) of adequate LDL-C control (<55 mg/dL) at 8 weeks. Adding bempedoic acid to statin–ezetimibe therapy in the setting of ACS is safe but failed to improve the percentage of patients achieving the LDL-C goal (<55 mg/dL) at 8 weeks. Larger, randomized studies are needed to confirm our findings. REGISTRATION: URL: https://www.clinicaltrialsregister.eu ; Unique identifier: 2021-006550-31.

Article Details

Journal Circulation
Volume / Issue Vol. 153, Issue 3
Published January 20, 2026
Pages 140-149
ISSN 0009-7322
Publisher Lippincott Williams & Wilkins

Journal Info

Circulation

Lippincott Williams & Wilkins

ISSN: 0009-7322 Health Sciences

Authors (35)

S

Sergio Raposeiras-Roubín

Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid

E

Emad Abu Assi

Povisa Hospital, Vigo, Spain (E.A.A.)

C

César Jiménez Méndez

Cardiology Department, University Hospital Puerta del Mar, Cádiz, Spain (C.J.M., A.V.R., M.T.G.G., J.A.P.d.l.M.)

E

Ester Mínguez de la Guía

Cardiology Department, University Hospital of Albacete, Spain (E.M.d.l.G., M.L.V., F.S.M., M.C.-P.)

J

José Ángel Pérez Rivera

Cardiology Department, University Hospital of Burgos, Spain (J.Á.P.R., L.A.I., A.M.M., E.S.C., I.S.S.)

M

Marta Marcos Mangas

Cardiology Department, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain (M.M.M., Á.V.H.-M., A.A.-S.)

A

Ana Ayesta

Cardiology Department, University Hospital Central de Asturias, Oviedo, Spain (A.A., A.A. Andrémar, J.R.)

A

Aitor Uribarri

Cardiology Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain (A.U., M.V.-B.).

P

Pablo Jorge Pérez

Cardiology Department, University Hospital of Canarias, Tenerife, Spain (P.J.P., M.M.M.C.)

P

Pablo José Antúnez Muinos

Cardiology Department, University Hospital Montecelo, Pontevedra, Spain (P.J.A.M., M.C.G.C.)

C

Clara Bonanad Lozano

Cardiology Department, University Clinical Hospital of Valencia and INCLIVA Health Research Institute, Spain (C.B.L., D.B.)

A

Anna Carrasquer

Hospital Universitari Joan XXIII, Tarragona, Spain

A

Ana Viana-Tejedor

Cardiology Department, University Hospital Joan XXIII of Tarragona, Spain (A.C.)

P

Pablo Domínguez Erquicia

Cardiology Department, University Hospital Álvaro Cunqueiro and Instituto de Investigación Sanitaria Galicia Sur, Vigo, Spain (S.R.R., P.D.E., A.A. Abejón, A.I.R.)

A

Alberto Villar Ruiz

Cardiology Department, University Hospital Puerta del Mar, Cádiz, Spain (C.J.M., A.V.R., M.T.G.G., J.A.P.d.l.M.)

M

Macarena López Vázquez

Cardiology Department, University Hospital of Albacete, Spain (E.M.d.l.G., M.L.V., F.S.M., M.C.-P.)

L

Lara Aguilar Iglesias

Cardiology Department, University Hospital of Burgos, Spain (J.Á.P.R., L.A.I., A.M.M., E.S.C., I.S.S.)

A

Alberto Alén Andrémar

Cardiology Department, University Hospital Álvaro Cunqueiro and Instituto de Investigación Sanitaria Galicia Sur, Vigo, Spain (S.R.R., P.D.E., A.A. Abejón, A.I.R.)

M

Maria Vidal Burdeus

Cardiology Department, University Hospital Vall D’Hebron, Barcelona, Spain (A.U., M.V.B.)

M

Marta Maria Martin Cabeza

Cardiology Department, University Hospital of Canarias, Tenerife, Spain (P.J.P., M.M.M.C.)

M

María Cristina González Cambeiro

Cardiology Department, University Hospital Montecelo, Pontevedra, Spain (P.J.A.M., M.C.G.C.)

D

Daznia Bompart

Cardiology Department, University Clinical Hospital of Valencia and INCLIVA Health Research Institute, Spain (C.B.L., D.B.)

J

Juan Carlos Gómez Polo

Cardiology Department, University Clinical Hospital San Carlos, Madrid, Spain (A.V.-T., J.C.G.P.).

M

Marina Teresa García García

Cardiology Department, University Hospital Puerta del Mar, Cádiz, Spain (C.J.M., A.V.R., M.T.G.G., J.A.P.d.l.M.)

A

Ana Merino Merino

Cardiology Department, University Hospital of Burgos, Spain (J.Á.P.R., L.A.I., A.M.M., E.S.C., I.S.S.)

J

José Rozado

Cardiology Department, University Hospital Central de Asturias, Oviedo, Spain (A.A., A.A. Andrémar, J.R.)

J

José Antonio Panera de la Mano

Cardiology Department, University Hospital Puerta del Mar, Cádiz, Spain (C.J.M., A.V.R., M.T.G.G., J.A.P.d.l.M.)

F

Francisco Salmerón Martínez

Cardiology Department, University Hospital of Albacete, Spain (E.M.d.l.G., M.L.V., F.S.M., M.C.-P.)

E

Ester Sánchez Corral

Cardiology Department, University Hospital of Burgos, Spain (J.Á.P.R., L.A.I., A.M.M., E.S.C., I.S.S.)

I

Isabel Santos Sánchez

Cardiology Department, University Hospital of Burgos, Spain (J.Á.P.R., L.A.I., A.M.M., E.S.C., I.S.S.)

Ángel Víctor Hernández-Martos

Cardiology Department, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain (M.M.M., Á.V.H.-M., A.A.-S.)

A

Andrés Antelo Abejón

Cardiology Department, University Hospital Álvaro Cunqueiro and Instituto de Investigación Sanitaria Galicia Sur, Vigo, Spain (S.R.R., P.D.E., A.A. Abejón, A.I.R.)

A

Andrés Iñiguez Romo

Cardiology Department, University Hospital Álvaro Cunqueiro and Instituto de Investigación Sanitaria Galicia Sur, Vigo, Spain (S.R.R., P.D.E., A.A. Abejón, A.I.R.)

M

Miguel Corbi-Pascual

Cardiology Department, University Hospital of Albacete, Spain (E.M.d.l.G., M.L.V., F.S.M., M.C.-P.)

A

Albert Ariza-Solé

Cardiology Department, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain (M.M.M., Á.V.H.-M., A.A.-S.)