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The goal of this clinical trial is to evaluate whether triple lipid-lowering therapy (atorvastatin, ezetimibe, and bempedoic acid) is more effective than dual therapy (atorvastatin and ezetimibe) in reducing LDL cholesterol levels in adults with acute coronary syndrome. It will also assess the safety of the treatment.
The main questions it aims to answer are:
Researchers will compare triple therapy to dual therapy to determine its effectiveness in lowering LDL-C levels.
Participants will:
Acute coronary syndrome (ACS) is a major cause of morbidity and mortality worldwide and is associated with a high risk of recurrent cardiovascular events. Aggressive lipid-lowering therapy, particularly reduction of low-density lipoprotein cholesterol (LDL-C), plays a central role in secondary prevention. Although high-intensity statins are the cornerstone of therapy, many patients fail to achieve target LDL-C levels, necessitating the addition of other lipid-lowering agents.
Ezetimibe, a cholesterol absorption inhibitor, has been shown to further reduce LDL-C levels when combined with statins. Bempedoic acid, a newer lipid-lowering agent that inhibits ATP citrate lyase, offers an additional mechanism to reduce cholesterol synthesis and may provide incremental benefits when added to standard therapy. However, limited evidence exists regarding the combined use of atorvastatin, ezetimibe, and bempedoic acid in patients with ACS.
This randomized controlled trial aims to compare the efficacy and safety of triple lipid-lowering therapy (atorvastatin, ezetimibe, and bempedoic acid) versus dual therapy (atorvastatin and ezetimibe) in patients with ACS. Eligible participants will be randomly assigned in a 1:1 ratio to receive either dual therapy or triple therapy. The intervention period will be three months.
The primary outcome of the study is the change in LDL-C levels from baseline to 3 months. Secondary outcomes include percentage reduction in LDL-C, changes in total cholesterol levels, proportion of patients achieving target LDL-C levels (<70 mg/dL), and incidence of adverse drug reactions.
Participants will undergo baseline clinical evaluation and laboratory investigations, including lipid profile assessment. Follow-up assessments will be conducted during the study period to monitor treatment response and safety. At the end of the study period, lipid levels and clinical outcomes will be reassessed and compared between the two groups.
This study is expected to provide evidence on whether adding bempedoic acid to standard dual lipid-lowering therapy offers superior LDL-C reduction and improved clinical outcomes in patients with ACS.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dual Therapy Group | Experimental | Participants will receive dual lipid-lowering therapy consisting of atorvastatin and ezetimibe for a duration of 6 weeks. |
|
| Triple Therapy Group | Experimental | Participants will receive triple lipid-lowering therapy consisting of atorvastatin, ezetimibe, and bempedoic acid for a duration of 3 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atorvastatin 40 Mg Oral Tablet | Drug | Atorvastatin administered orally once daily as part of lipid-lowering therapy |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in LDL cholesterol level | Change in low-density lipoprotein cholesterol (LDL-C) measured in mg/dL from baseline to 3 months after initiation of therapy. | Baseline to 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of adverse drug reactions | Number of participants experiencing adverse drug reactions during the study period. | 3 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Usman Sajid, MBBS, Resident cardiologist | Contact | +923028169194 | thextremefire@gmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Punjab Institute of Cardiology | Lahore | Punjab Province | 56000 | Pakistan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41200807 | Background | Raposeiras-Roubin S, Abu Assi E, Jimenez Mendez C, Minguez de la Guia E, Perez Rivera JA, Marcos Mangas M, Ayesta A, Uribarri A, Jorge Perez P, Antunez Muinos PJ, Bonanad Lozano C, Carrasquer A, Viana-Tejedor A, Dominguez Erquicia P, Villar Ruiz A, Lopez Vazquez M, Aguilar Iglesias L, Alen Andremar A, Vidal Burdeus M, Martin Cabeza MM, Gonzalez Cambeiro MC, Bompart D, Gomez Polo JC, Garcia Garcia MT, Merino Merino A, Rozado J, Panera de la Mano JA, Salmeron Martinez F, Sanchez Corral E, Santos Sanchez I, Hernandez-Martos AV, Antelo Abejon A, Iniguez Romo A, Corbi-Pascual M, Ariza-Sole A. Triple Versus Dual Lipid-Lowering Therapy in Acute Coronary Syndrome: The ES-BempedACS Randomized Clinical Trial. Circulation. 2026 Jan 20;153(3):140-149. doi: 10.1161/CIRCULATIONAHA.125.075388. Epub 2025 Nov 7. |
| Label | URL |
|---|---|
| This landmark trial showed that adding ezetimibe to statin further lowers LDL and improves cardiovascular outcomes | View source |
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Individual participant data (IPD) will not be shared.
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| ID | Term |
|---|---|
| D054058 | Acute Coronary Syndrome |
| D006937 | Hypercholesterolemia |
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D000069059 | Atorvastatin |
| D013607 | Tablets |
| D000069438 | Ezetimibe |
| C581236 | 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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Participants will be randomly assigned in a 1:1 ratio to receive either dual lipid-lowering therapy (atorvastatin and ezetimibe) or triple lipid-lowering therapy (atorvastatin, ezetimibe, and bempedoic acid).
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This is an open-label study in which both participants and investigators will be aware of the assigned treatment groups.
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| Ezetimibe 10 mg | Drug | Ezetimibe administered orally once daily to reduce cholesterol absorption |
|
| Bempedoic Acid 180 MG Oral Tablet | Drug | Bempedoic acid administered orally once daily as an adjunct lipid-lowering agent |
|
| This trial showed that adding Bempidoic acid to statin therapy further lowers LDL and improves cardiovascular outcomes | View source |
| D006949 |
| Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D006538 |
| Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
| D001384 | Azetidines |
| D001385 | Azetines |