Abstract
The plasma levels of high-density lipoprotein (HDL) cholesterol are inversely related to cardiovascular risk. Traditional HDL-raising therapies, like fibrates, PPAR-γ agonists, and nicacin, among others, are associated with undesirable side effects, limited efficacy, or have not yet been shown to improve morbidity and mortality on top of statins in clinical outcome trials. A novel pharmacological target for raising circulating HDL-C levels is the cholesterol ester transfer protein (CETP), an enzyme that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins. Four pharmacological small-molecule inhibitors of CETP, i.e. torcetrapib (Pfizer), dalcetrapib (JTT-705; Roche), anacetrapib (Merck), and evacetrapib (Eli Lilly) have been developed. Notwithstanding a marked increase in HDL, torcetrapib was associated with an increase in all-cause mortality in the ILLUMINATE trial and raised safety concerns related to the off-target effects of CETP inhibition. Most recently, development of dalcetrapib was abruptly stopped due to a lack of clinically meaningful efficacy. Thus, it will be of utmost importance to demonstrate that the remaining CETP inhibitors in development not only increase HDL-C levels in plasma, but also improve HDL-function in patients with coronary disease or an acute coronary syndrome.
Keywords: HDL, CETP, clinical outcomes, endothelial function
Current Vascular Pharmacology
Title:Therapeutic Targets to Raise HDL in Patients at Risk or with Coronary Artery Disease
Volume: 10 Issue: 6
Author(s): Thomas F. Luscher, Arnold von Eckardstein and Branko Simic
Affiliation:
Keywords: HDL, CETP, clinical outcomes, endothelial function
Abstract: The plasma levels of high-density lipoprotein (HDL) cholesterol are inversely related to cardiovascular risk. Traditional HDL-raising therapies, like fibrates, PPAR-γ agonists, and nicacin, among others, are associated with undesirable side effects, limited efficacy, or have not yet been shown to improve morbidity and mortality on top of statins in clinical outcome trials. A novel pharmacological target for raising circulating HDL-C levels is the cholesterol ester transfer protein (CETP), an enzyme that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins. Four pharmacological small-molecule inhibitors of CETP, i.e. torcetrapib (Pfizer), dalcetrapib (JTT-705; Roche), anacetrapib (Merck), and evacetrapib (Eli Lilly) have been developed. Notwithstanding a marked increase in HDL, torcetrapib was associated with an increase in all-cause mortality in the ILLUMINATE trial and raised safety concerns related to the off-target effects of CETP inhibition. Most recently, development of dalcetrapib was abruptly stopped due to a lack of clinically meaningful efficacy. Thus, it will be of utmost importance to demonstrate that the remaining CETP inhibitors in development not only increase HDL-C levels in plasma, but also improve HDL-function in patients with coronary disease or an acute coronary syndrome.
Export Options
About this article
Cite this article as:
F. Luscher Thomas, von Eckardstein Arnold and Simic Branko, Therapeutic Targets to Raise HDL in Patients at Risk or with Coronary Artery Disease, Current Vascular Pharmacology 2012; 10 (6) . https://dx.doi.org/10.2174/157016112803520972
DOI https://dx.doi.org/10.2174/157016112803520972 |
Print ISSN 1570-1611 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6212 |
Call for Papers in Thematic Issues
Ischemic Cardiovascular Diseases: Mechanisms, Diagnosis and Therapy
Ischemic cardiovascular disease includes myocardial infarction, coronary atherosclerotic heart disease, angina pectoris, etc., constitute the leading cause of patient mortality by preventing tissues from getting sufficient oxygen and nutrients. Ischemic heart disease, as a clinical condition, is characterized by myocardial ischemia, causing an imbalance between myocardial blood supply and demand, ...read more
TREATMENT OF CARDIOVASCULAR DISEASE IN CHRONIC AND END STAGE KIDNEY DISEASE
Cardiovascular disease still remains the leading cause of death in Chronic and End Stage Kidney Disease, accounting for more than half of all deaths in dialysis patients. During the past decade, research has been focused on novel therapeutic agents that might delay or even reverse cardiovascular disease and vascular calcification, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Biomarkers in Systemic Sclerosis-Related Pulmonary Arterial Hypertension
Current Vascular Pharmacology Energy Metabolism in the Normal and in the Diabetic Heart
Current Pharmaceutical Design How Effective are the Lipid Modifying Medicines at Preventing Coronary Heart Disease in Patients with the Metabolic Syndrome?
Vascular Disease Prevention (Discontinued) Patent Selections
Recent Patents on Cardiovascular Drug Discovery Subject Index to Volume 1
Current Pharmacogenomics Mitochondrial Tolerance to Drugs and Toxic Agents in Ageing and Disease
Current Drug Targets Advances in Stem Cells Transplantation for the Therapy of Parkinson’s Disease
Current Stem Cell Research & Therapy Oxidative Stress During Myocardial Ischaemia and Heart Failure
Current Pharmaceutical Design Functional Recovery After Stroke: A Review of Current Developments in Stroke Rehabilitation Research
Reviews on Recent Clinical Trials A Review of Feature Extraction from ECG Signals and Classification/ Detection for Ventricular Arrhythmias
Recent Advances in Computer Science and Communications Are Cerebrovascular White Matter Lesions an Early Sign of Vascular Cognitive Impairment and Vascular Dementia?
Vascular Disease Prevention (Discontinued) Nutrient and Qualitative Phytochemical Analysis-evaluation of Antimicrobial Activity and Development of Products with Mulberry Leaves (<i>Mulberry indica</i> L.)
Current Nutrition & Food Science Early Functional and Structural Microvascular Changes in Hypertension Related to Aging
Current Hypertension Reviews Noninvasive Diagnosis of Chemotherapy Related Cardiotoxicity
Current Cardiology Reviews Prostacyclin, Atherothrombosis and Diabetes Mellitus: Physiologic and Clinical Considerations
Current Molecular Medicine Gastrointestinal Bleeding Associated With Warfarin and Rivaroxaban Therapy in Atrial Fibrillation Cases with Concomitant Coagulopathy
Cardiovascular & Hematological Disorders-Drug Targets Molecular Modeling Investigation of Folic Acid Conjugation to MDM2 Inhibitors for Enhanced Cellular Uptake and Target Binding
Current Computer-Aided Drug Design Salusins in Hypertension and Related Cardiovascular Diseases
Current Drug Metabolism Fullerenes for Cancer Diagnosis and Therapy: Preparation, Biological and Clinical Perspectives
Current Drug Metabolism Cardiac Autonomic Nervous System in Heart Failure: Imaging Technique and Clinical Implications
Current Cardiology Reviews