Rationale and design of REDUCE‐IT: Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial

Residual cardiovascular risk persists despite statins, yet outcome studies of lipid‐targeted therapies beyond low‐density lipoprotein cholesterol (LDL‐C) have not demonstrated added benefit. Triglyceride elevation is an independent risk factor for cardiovascular events. High‐dose eicosapentaenoic ac...

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Veröffentlicht in:Clinical cardiology (Mahwah, N.J.) Jg. 40; H. 3; S. 138 - 148
Hauptverfasser: Bhatt, Deepak L., Steg, Ph. Gabriel, Brinton, Eliot A., Jacobson, Terry A., Miller, Michael, Tardif, Jean‐Claude, Ketchum, Steven B., Doyle, Ralph T., Murphy, Sabina A., Soni, Paresh N., Braeckman, Rene A., Juliano, Rebecca A., Ballantyne, Christie M.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: New York Wiley Periodicals, Inc 01.03.2017
John Wiley & Sons, Inc
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ISSN:0160-9289, 1932-8737, 1932-8737
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Abstract Residual cardiovascular risk persists despite statins, yet outcome studies of lipid‐targeted therapies beyond low‐density lipoprotein cholesterol (LDL‐C) have not demonstrated added benefit. Triglyceride elevation is an independent risk factor for cardiovascular events. High‐dose eicosapentaenoic acid (EPA) reduces triglyceride‐rich lipoproteins without raising LDL‐C. Omega‐3s have postulated pleiotropic cardioprotective benefits beyond triglyceride‐lowering. To date, no large, multinational, randomized clinical trial has proved that lowering triglycerides on top of statin therapy improves cardiovascular outcomes. The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE‐IT; NCT01492361) is a phase 3b randomized, double‐blinded, placebo‐controlled trial of icosapent ethyl, a highly purified ethyl ester of EPA, vs placebo. The main objective is to evaluate whether treatment with icosapent ethyl reduces ischemic events in statin‐treated patients with high triglycerides at elevated cardiovascular risk. REDUCE‐IT enrolled men or women age ≥45 years with established cardiovascular disease or age ≥50 years with diabetes mellitus and 1 additional risk factor. Randomization required fasting triglycerides ≥150 mg/dL and <500 mg/dL and LDL‐C >40 mg/dL and ≤100 mg/dL with stable statin (± ezetimibe) ≥4 weeks prior to qualifying measurements. The primary endpoint is a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary endpoint is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Several secondary, tertiary, and exploratory endpoints will be assessed. Approximately 8000 patients have been randomized at approximately 470 centers worldwide. Follow‐up will continue in this event‐driven trial until approximately 1612 adjudicated primary‐efficacy endpoint events have occurred.
AbstractList Residual cardiovascular risk persists despite statins, yet outcome studies of lipid-targeted therapies beyond low-density lipoprotein cholesterol (LDL-C) have not demonstrated added benefit. Triglyceride elevation is an independent risk factor for cardiovascular events. High-dose eicosapentaenoic acid (EPA) reduces triglyceride-rich lipoproteins without raising LDL-C. Omega-3s have postulated pleiotropic cardioprotective benefits beyond triglyceride-lowering. To date, no large, multinational, randomized clinical trial has proved that lowering triglycerides on top of statin therapy improves cardiovascular outcomes. The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT; NCT01492361) is a phase 3b randomized, double-blinded, placebo-controlled trial of icosapent ethyl, a highly purified ethyl ester of EPA, vs placebo. The main objective is to evaluate whether treatment with icosapent ethyl reduces ischemic events in statin-treated patients with high triglycerides at elevated cardiovascular risk. REDUCE-IT enrolled men or women age ≥45years with established cardiovascular disease or age ≥50years with diabetes mellitus and 1 additional risk factor. Randomization required fasting triglycerides ≥150mg/dL and <500mg/dL and LDL-C >40mg/dL and ≤100mg/dL with stable statin (± ezetimibe) ≥4weeks prior to qualifying measurements. The primary endpoint is a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary endpoint is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Several secondary, tertiary, and exploratory endpoints will be assessed. Approximately 8000 patients have been randomized at approximately 470 centers worldwide. Follow-up will continue in this event-driven trial until approximately 1612 adjudicated primary-efficacy endpoint events have occurred.
Residual cardiovascular risk persists despite statins, yet outcome studies of lipid‐targeted therapies beyond low‐density lipoprotein cholesterol ( LDL ‐C) have not demonstrated added benefit. Triglyceride elevation is an independent risk factor for cardiovascular events. High‐dose eicosapentaenoic acid ( EPA ) reduces triglyceride‐rich lipoproteins without raising LDL ‐C. Omega‐3s have postulated pleiotropic cardioprotective benefits beyond triglyceride‐lowering. To date, no large, multinational, randomized clinical trial has proved that lowering triglycerides on top of statin therapy improves cardiovascular outcomes. The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial ( REDUCE‐IT ; NCT01492361 ) is a phase 3b randomized, double‐blinded, placebo‐controlled trial of icosapent ethyl, a highly purified ethyl ester of EPA , vs placebo. The main objective is to evaluate whether treatment with icosapent ethyl reduces ischemic events in statin‐treated patients with high triglycerides at elevated cardiovascular risk. REDUCE‐IT enrolled men or women age ≥45 years with established cardiovascular disease or age ≥50 years with diabetes mellitus and 1 additional risk factor. Randomization required fasting triglycerides ≥150 mg/ dL and <500 mg/ dL and LDL ‐C >40 mg/ dL and ≤100 mg/ dL with stable statin (± ezetimibe) ≥4 weeks prior to qualifying measurements. The primary endpoint is a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary endpoint is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Several secondary, tertiary, and exploratory endpoints will be assessed. Approximately 8000 patients have been randomized at approximately 470 centers worldwide. Follow‐up will continue in this event‐driven trial until approximately 1612 adjudicated primary‐efficacy endpoint events have occurred.
Residual cardiovascular risk persists despite statins, yet outcome studies of lipid-targeted therapies beyond low-density lipoprotein cholesterol (LDL-C) have not demonstrated added benefit. Triglyceride elevation is an independent risk factor for cardiovascular events. High-dose eicosapentaenoic acid (EPA) reduces triglyceride-rich lipoproteins without raising LDL-C. Omega-3s have postulated pleiotropic cardioprotective benefits beyond triglyceride-lowering. To date, no large, multinational, randomized clinical trial has proved that lowering triglycerides on top of statin therapy improves cardiovascular outcomes. The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT; NCT01492361) is a phase 3b randomized, double-blinded, placebo-controlled trial of icosapent ethyl, a highly purified ethyl ester of EPA, vs placebo. The main objective is to evaluate whether treatment with icosapent ethyl reduces ischemic events in statin-treated patients with high triglycerides at elevated cardiovascular risk. REDUCE-IT enrolled men or women age ≥45 years with established cardiovascular disease or age ≥50 years with diabetes mellitus and 1 additional risk factor. Randomization required fasting triglycerides ≥150 mg/dL and <500 mg/dL and LDL-C >40 mg/dL and ≤100 mg/dL with stable statin (± ezetimibe) ≥4 weeks prior to qualifying measurements. The primary endpoint is a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary endpoint is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Several secondary, tertiary, and exploratory endpoints will be assessed. Approximately 8000 patients have been randomized at approximately 470 centers worldwide. Follow-up will continue in this event-driven trial until approximately 1612 adjudicated primary-efficacy endpoint events have occurred.Residual cardiovascular risk persists despite statins, yet outcome studies of lipid-targeted therapies beyond low-density lipoprotein cholesterol (LDL-C) have not demonstrated added benefit. Triglyceride elevation is an independent risk factor for cardiovascular events. High-dose eicosapentaenoic acid (EPA) reduces triglyceride-rich lipoproteins without raising LDL-C. Omega-3s have postulated pleiotropic cardioprotective benefits beyond triglyceride-lowering. To date, no large, multinational, randomized clinical trial has proved that lowering triglycerides on top of statin therapy improves cardiovascular outcomes. The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT; NCT01492361) is a phase 3b randomized, double-blinded, placebo-controlled trial of icosapent ethyl, a highly purified ethyl ester of EPA, vs placebo. The main objective is to evaluate whether treatment with icosapent ethyl reduces ischemic events in statin-treated patients with high triglycerides at elevated cardiovascular risk. REDUCE-IT enrolled men or women age ≥45 years with established cardiovascular disease or age ≥50 years with diabetes mellitus and 1 additional risk factor. Randomization required fasting triglycerides ≥150 mg/dL and <500 mg/dL and LDL-C >40 mg/dL and ≤100 mg/dL with stable statin (± ezetimibe) ≥4 weeks prior to qualifying measurements. The primary endpoint is a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary endpoint is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Several secondary, tertiary, and exploratory endpoints will be assessed. Approximately 8000 patients have been randomized at approximately 470 centers worldwide. Follow-up will continue in this event-driven trial until approximately 1612 adjudicated primary-efficacy endpoint events have occurred.
Residual cardiovascular risk persists despite statins, yet outcome studies of lipid‐targeted therapies beyond low‐density lipoprotein cholesterol (LDL‐C) have not demonstrated added benefit. Triglyceride elevation is an independent risk factor for cardiovascular events. High‐dose eicosapentaenoic acid (EPA) reduces triglyceride‐rich lipoproteins without raising LDL‐C. Omega‐3s have postulated pleiotropic cardioprotective benefits beyond triglyceride‐lowering. To date, no large, multinational, randomized clinical trial has proved that lowering triglycerides on top of statin therapy improves cardiovascular outcomes. The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE‐IT; NCT01492361) is a phase 3b randomized, double‐blinded, placebo‐controlled trial of icosapent ethyl, a highly purified ethyl ester of EPA, vs placebo. The main objective is to evaluate whether treatment with icosapent ethyl reduces ischemic events in statin‐treated patients with high triglycerides at elevated cardiovascular risk. REDUCE‐IT enrolled men or women age ≥45 years with established cardiovascular disease or age ≥50 years with diabetes mellitus and 1 additional risk factor. Randomization required fasting triglycerides ≥150 mg/dL and <500 mg/dL and LDL‐C >40 mg/dL and ≤100 mg/dL with stable statin (± ezetimibe) ≥4 weeks prior to qualifying measurements. The primary endpoint is a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary endpoint is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Several secondary, tertiary, and exploratory endpoints will be assessed. Approximately 8000 patients have been randomized at approximately 470 centers worldwide. Follow‐up will continue in this event‐driven trial until approximately 1612 adjudicated primary‐efficacy endpoint events have occurred.
Author Murphy, Sabina A.
Jacobson, Terry A.
Ballantyne, Christie M.
Braeckman, Rene A.
Steg, Ph. Gabriel
Brinton, Eliot A.
Soni, Paresh N.
Juliano, Rebecca A.
Doyle, Ralph T.
Miller, Michael
Ketchum, Steven B.
Bhatt, Deepak L.
Tardif, Jean‐Claude
AuthorAffiliation 1 Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School Boston Massachusetts
8 Amarin Pharma Inc. Bedminster New Jersey
11 TIMI Study Group, Cardiovascular Division, Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts
5 Office of Health Promotion and Disease Prevention, Department of Medicine Emory University School of Medicine Atlanta Georgia
12 Department of Medicine, Baylor College of Medicine, and Center for Cardiovascular Disease Prevention Methodist DeBakey Heart and Vascular Center Houston Texas
4 Utah Foundation for Biomedical Research, and Utah Lipid Center Salt Lake City
10 KemPharm, Inc., Celebration Florida
3 NHLI, Imperial College Royal Brompton Hospital London United Kingdom
6 Department of Medicine University of Maryland School of Medicine Baltimore
7 Montreal Heart Institute Université de Montréal Québec Canada
2 FACT (French Alliance for Cardiovascular Trials), an F‐CRIN network, Département Hospitalo‐Univ
AuthorAffiliation_xml – name: 12 Department of Medicine, Baylor College of Medicine, and Center for Cardiovascular Disease Prevention Methodist DeBakey Heart and Vascular Center Houston Texas
– name: 3 NHLI, Imperial College Royal Brompton Hospital London United Kingdom
– name: 10 KemPharm, Inc., Celebration Florida
– name: 9 Albireo Pharma Boston Massachusetts
– name: 2 FACT (French Alliance for Cardiovascular Trials), an F‐CRIN network, Département Hospitalo‐Universitaire FIRE, AP‐HP, Hôpital Bichat Université Paris‐Diderot, INSERM U‐1148 Paris France
– name: 4 Utah Foundation for Biomedical Research, and Utah Lipid Center Salt Lake City
– name: 5 Office of Health Promotion and Disease Prevention, Department of Medicine Emory University School of Medicine Atlanta Georgia
– name: 8 Amarin Pharma Inc. Bedminster New Jersey
– name: 6 Department of Medicine University of Maryland School of Medicine Baltimore
– name: 11 TIMI Study Group, Cardiovascular Division, Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts
– name: 1 Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School Boston Massachusetts
– name: 7 Montreal Heart Institute Université de Montréal Québec Canada
Author_xml – sequence: 1
  givenname: Deepak L.
  orcidid: 0000-0002-1278-6245
  surname: Bhatt
  fullname: Bhatt, Deepak L.
  organization: Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School
– sequence: 2
  givenname: Ph. Gabriel
  surname: Steg
  fullname: Steg, Ph. Gabriel
  organization: Royal Brompton Hospital
– sequence: 3
  givenname: Eliot A.
  surname: Brinton
  fullname: Brinton, Eliot A.
  organization: Utah Foundation for Biomedical Research, and Utah Lipid Center
– sequence: 4
  givenname: Terry A.
  surname: Jacobson
  fullname: Jacobson, Terry A.
  organization: Emory University School of Medicine
– sequence: 5
  givenname: Michael
  surname: Miller
  fullname: Miller, Michael
  organization: University of Maryland School of Medicine
– sequence: 6
  givenname: Jean‐Claude
  surname: Tardif
  fullname: Tardif, Jean‐Claude
  organization: Université de Montréal
– sequence: 7
  givenname: Steven B.
  surname: Ketchum
  fullname: Ketchum, Steven B.
  organization: Amarin Pharma Inc
– sequence: 8
  givenname: Ralph T.
  surname: Doyle
  fullname: Doyle, Ralph T.
  organization: Amarin Pharma Inc
– sequence: 9
  givenname: Sabina A.
  surname: Murphy
  fullname: Murphy, Sabina A.
  organization: Brigham and Women's Hospital and Harvard Medical School
– sequence: 10
  givenname: Paresh N.
  surname: Soni
  fullname: Soni, Paresh N.
  organization: Albireo Pharma
– sequence: 11
  givenname: Rene A.
  surname: Braeckman
  fullname: Braeckman, Rene A.
  organization: KemPharm, Inc., Celebration
– sequence: 12
  givenname: Rebecca A.
  surname: Juliano
  fullname: Juliano, Rebecca A.
  organization: Amarin Pharma Inc
– sequence: 13
  givenname: Christie M.
  surname: Ballantyne
  fullname: Ballantyne, Christie M.
  organization: Methodist DeBakey Heart and Vascular Center
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28294373$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright 2017 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.
2017 Wiley Periodicals, Inc.
Copyright_xml – notice: 2017 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.
– notice: 2017 Wiley Periodicals, Inc.
CorporateAuthor on behalf of the REDUCE‐IT Investigators
REDUCE-IT Investigators
CorporateAuthor_xml – name: on behalf of the REDUCE‐IT Investigators
– name: REDUCE-IT Investigators
DBID 24P
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Keywords Clinical trials
General clinical cardiology/adult
Lipidology
Language English
License Attribution-NonCommercial
http://creativecommons.org/licenses/by-nc/4.0
2017 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.
This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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Snippet Residual cardiovascular risk persists despite statins, yet outcome studies of lipid‐targeted therapies beyond low‐density lipoprotein cholesterol (LDL‐C) have...
Residual cardiovascular risk persists despite statins, yet outcome studies of lipid‐targeted therapies beyond low‐density lipoprotein cholesterol ( LDL ‐C)...
Residual cardiovascular risk persists despite statins, yet outcome studies of lipid-targeted therapies beyond low-density lipoprotein cholesterol (LDL-C) have...
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SubjectTerms Cardiovascular Diseases - drug therapy
Cardiovascular Diseases - epidemiology
Clinical trials
Dose-Response Relationship, Drug
Double-Blind Method
Eicosapentaenoic Acid - administration & dosage
Eicosapentaenoic Acid - analogs & derivatives
Female
Follow-Up Studies
France - epidemiology
General clinical cardiology/adult
Health risk assessment
Heart attacks
Humans
Incidence
Lipidology
Low density lipoprotein
Male
Middle Aged
Platelet Aggregation Inhibitors - administration & dosage
Prospective Studies
Quebec - epidemiology
Risk Factors
Time Factors
Treatment Outcome
Trial Designs
Triglycerides
United Kingdom - epidemiology
United States - epidemiology
Title Rationale and design of REDUCE‐IT: Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fclc.22692
https://www.ncbi.nlm.nih.gov/pubmed/28294373
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