FOURIER (TIMI 59) / EBBINGHAUS

FOURIER (TIMI 59) was a double-blind, randomized, placebo-controlled, multicenter study assessing the Impact of additional LDL-cholesterol reduction on major cardiovascular events when AMG 145 is used in combination with statin therapy in patients with clinically evident cardiovascular disease.  EBBINGHAUS was a cognitive study of patients enrolled in the FOURIER trial.

MAIN RESULTS:
Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease

N Engl J Med. 2017 May 4;376(18):1713-1722.

MAIN RESULTS PRESENTATIONS

FOURIER Main Results (Sabatine, ACC 2017)
EBBINGHAUS Main Results (Giugliano, ACC 2017)

PRESENTATIONS

Maximum Intensity Statin (Sabatine, NLA 2017)
Achieved LDL-C (Giugliano, ESC 2017)
Stroke (Pederson, ESC 2017)
Diabetes (Sabatine, EASD 2017)
PAD (Bonaca, AHA 2017)
MI Subgroup (Sabatine, AHA 2017)
Total Events (Murphy, AHA 2017)
MI Size and Type (Wiviott, AHA 2017)
Risk Score (Bohula, AHA 2017)
Variability in Evolocumab (Qamar, ACC 2018)
Inflammatory and Cholestrol Risk (Bohula, ACC 2018)
Martin Hopkins LDL-C (Martin, NLA 2018)
Lp(a) in FOURIER (O’Donoghue, EAS 2018)
Age and Sex (Sever, ESC 2018)
FOURIER Cognition Poster (Gencer, AHA 2019)
FOURIER Genetics (Marston, AHA 2019)
FOURIER Recent MI Poster (Gencer, AHA 2019)
Performance Of A Novel Genetic Risk Score To Identify Risk Of VTE In Patients With Cardiometabolic Disease (Marston, ACC 2020)
PCSK9 Inhibition And Aortic Stenosis In The FOURIER Trial (Bergmark, ACC 2020)
Efficacy of Lowering Low-Density Lipoprotein Cholesterol in Older Patients (Gencer, AHA 2020)
Relationship Between Baseline LDL-C and %LDL-C Reduction with Evolocumab in the FOURIER Trial (Marcusa, AHA 2020)
Reduction with Evolocumab in Complex Coronary Revascularization (Oyama, AHA 2020)
A Novel Genetic Risk Score Predicts Ischemic Stroke in Patients with Cardiometabolic Disease (Patel, AHA 2020)
Cardiovascular Outcomes in Patients with Established Atherosclerosis and LDLR Loss of Function (Marston, AHA 2020)
Combining High-Sensitivity Troponin with the AHA/ACC Cholesterol Guidelines To Guide Evolocumab Therapy (Marston, AHA 2020)
Effects of Evolocumab in Patients with Prior Percutaneous Coronary Intervention (Furtado, AHA 2020)
Biomarker prediction of major coronary events and complex revascularization procedures in patients with stable atherosclerosis (Fagundes, Jr., ACC 2021)
Acute arterial events across all vascular territories in the FOURIER trial (Oyama, ESC 2021)
Cardiovascular Benefit of Lowering LDL-C Below ~1 mmol per L (40 mg per dl) (Marston, ESC 2021)
Clinical Applications of a Polygenic Risk Score to Predict Atrial Fibrillation in Patients with Cardiometabolic Disease (Garfinkel, AHA 2021)
Clinical Safety Outcomes in Relation to Lipoprotein(a) Concentration. Insights from the FOURIER trial (Gencer, AHA 2021)
ApoB-containing Lipoproteins and Risk of Myocardial Infarction. Distinguishing between Particle Concentration, Type, and Content (Marston, AHA 2021)
A Genetic Risk Score to Predict Peripheral Artery Disease and Acute Limb Ischemia in Patients With Cardiometabolic Disease (Patel, AHA 2021)
Assessment of Atherothrombotic Risk in Patients with Type 2 Diabetes Mellitus (Berg, ACC 2022)
Development of a Novel Polygenic Risk Score to Predict Risk of Aortic Stenosis Events (Small, AHA 2022)
Type 2 Diabetes Mellitus Polygenic Score Predicts New Onset Diabetes in Patients With Established Atherosclerotic Cardiovascular Disease-A FOURIER Sub-Study (Moura, AHA 2022)
Cardiovascular Benefit of Lowering LDL-C Below 40 mg per dl (Marston, AHA 2022)
Association Between Achieved LDL-Cholesterol and Long-term Cardiovascular and Safety Outcomes – An Analysis of the FOURIER and FOURIER-OLE Studies (Gaba, AHA 2022)
Reduction in Total CV Events with the PCSK9 Inhibitor Evolocumab in Patients with Cardiovascular Disease in the Combined FOURIER and FOURIER OLE Studies (Murphy, ACC 2023)
Genetically Mediated Vascular Endothelial Cell Dysfunction and Its Dependence on Serum LDL-C Levels for the Development of Coronary Artery Atherosclerosis: Insights from the UK Biobank and FOURIER Trial (Marston, ACC 2023)
Risk Of Kidney Disease Progression And Efficacy Of SGLT2 Inhibition In Patients With Type 2 Diabetes Mellitus (Moura, ACC 2023)
Lipoprotein(a) and the risk of Major Adverse Limb Events in Patients with Stable Atherosclerotic Vascular Disease (Bonaca, ESC 2023)

OTHER PUBLICATIONS

Rationale and design of the Further cardiovascular OUtcomes Research with PCSK9 Inhibition in subjects with Elevated Risk trial. Am Heart J. 2016 Mar;173:94-101.

Design and rationale of the EBBINGHAUS trial: A phase 3, double-blind, placebo-controlled, multicenter study to assess the effect of evolocumab on cognitive function in patients with clinically evident cardiovascular disease and receiving statin background lipid-lowering therapy-A cognitive study of patients enrolled in the FOURIER trial. Clin Cardiol. 2017 Feb;40(2):59-65.

Cognitive Function in a Randomized Trial of Evolocumab. N Engl J Med. 2017 Aug 17;377(7):633-643.

Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial. Lancet. 2017 Oct 28;390(10106):1962-1971.

Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol. 2017 Dec;5(12):941-950.

Cost-effectiveness of Evolocumab Therapy for Reducing Cardiovascular Events in Patients With Atherosclerotic Cardiovascular Disease. JAMA Cardiol. 2017 Oct 1;2(10):1069-1078.

Low-Density Lipoprotein Cholesterol Lowering With Evolocumab and Outcomes in Patients With Peripheral Artery Disease: Insights From the FOURIER Trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). Circulation. 2018 Jan 23;137(4):338-350.

Clinical Efficacy and Safety of Evolocumab in High-Risk Patients Receiving a Statin: Secondary Analysis of Patients With Low LDL Cholesterol Levels and in Those Already Receiving a Maximal-Potency Statin in a Randomized Clinical Trial. JAMA Cardiol. 2017 Dec 1;2(12):1385-1391.

Inflammatory and Cholesterol Risk in the FOURIER Trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk). Circulation. 2018 Jul 10;138(2):131-140.

Comparison of Low-density Lipoprotein Cholesterol Assessment by Martin/Hopkins Estimation, Friedewald Estimation, and Preparative Ultracentrifugation: Insights From the FOURIER Trial. JAMA Cardiol. 2018 Aug 1;3(8):749-753.

Clinical Benefit of Evolocumab by Severity and Extent of Coronary Artery Disease: An Analysis from FOURIER. Circulation. 2018 Aug 21;138(8):756-766.

Efficacy and Safety of Further Lowering of Low-Density Lipoprotein Cholesterol in Patients Starting With Very Low Levels: A Meta-analysis. JAMA Cardiol. 2018 Sep 1;3(9):823-828. 

Interindividual Variation in Low-Density Lipoprotein Cholesterol Level Reduction With Evolocumab: An Analysis of FOURIER Trial Data. JAMA Cardiol. 2019 Jan 1;4(1):59-63.

Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk. Circulation. 2019 Mar 19;139(12):1483-1492.

Efficacy and Safety of Evolocumab in Chronic Kidney Disease in the FOURIER Trial. J Am Coll Cardiol. 2019 Jun 18;73(23):2961-2970.

Effect of the PCSK9 Inhibitor Evolocumab on Total Cardiovascular Events in Patients With Cardiovascular Disease: A Prespecified Analysis From the FOURIER Trial. JAMA Cardiol. 2019 Jul 1;4(7):613-619.

Correctly understanding the diabetes data in FOURIER. Diabetes Obes Metab. 2019 Oct;21(10):2342-2343.

Predicting Benefit From Evolocumab Therapy in Patients With Atherosclerotic Disease Using a Genetic Risk Score: Results From the FOURIER Trial. Circulation. 2020 Feb 25;141(8):616-623.

LDL-cholesterol lowering with evolocumab, and outcomes according to age and sex in patients in the FOURIER Trial. Eur J Prev Cardiol. 2020 Feb 4;2047487320902750. doi: 10.1177/2047487320902750.

What Lessons Have We Learned and What Remains to be Clarified for PCSK9 Inhibitors? A Review of FOURIER and ODYSSEY Outcomes Trials. Cardiol Ther. 2020 Jun;9(1):59-73.

The Effect of PCSK9 Inhibition on the Risk of Venous Thromboembolism. Circulation. 2020 May 19;141(20):1600-1607.

Stroke Prevention With the PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) Inhibitor Evolocumab Added to Statin in High-Risk Patients With Stable Atherosclerosis. Stroke. 2020 May;51(5):1546-1554.

Cognition After Lowering LDL-Cholesterol With Evolocumab. J Am Coll Cardiol. 2020 May 12;75(18):2283-2293.

An Exploratory Analysis of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition and Aortic Stenosis in the FOURIER Trial. JAMA Cardiol. 2020 Jun 1;5(6):709-713.

Effect of Evolocumab on Type and Size of Subsequent Myocardial Infarction: A Prespecified Analysis of the FOURIER Randomized Clinical Trial. JAMA Cardiol. 2020 Jul 1;5(7):787-793.

Efficacy of Evolocumab on Cardiovascular Outcomes in Patients With Recent Myocardial Infarction: A Prespecified Secondary Analysis From the FOURIER Trial. JAMA Cardiol. 2020 May 20;5(8):1-6.

Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials. Lancet. 2020 Nov 21;396(10263):1637-1643.

Association of Baseline Low-Density Lipoprotein Cholesterol and Percentage Low-Density Lipoprotein Cholesterol Reduction With Statins, Ezetimibe, and PCSK9 Inhibition. JAMA Cardiol. 2020 Nov 13;6(5):1-5.

Clinical Application of a Novel Genetic Risk Score for Ischemic Stroke in Patients with Cardiometabolic Disease. Circulation. 2021 Feb 2;143(5):470-478.

Effect of Evolocumab on Complex Coronary Disease Requiring Revascularization. J Am Coll Cardiol. 2021 Jan, 77 (3) 259–267.

Genetic Risk Score to Identify Risk of Venous Thromboembolism in Patients with Cardiometabolic Disease. Circ Genom Precis Med. 2021 Feb;14(1):e003006.

Efficacy and Safety of PCSK9 Inhibition With Evolocumab in Reducing Cardiovascular Events in Patients With Metabolic Syndrome Receiving Statin Therapy: Secondary Analysis From the FOURIER Randomized Clinical Trial. JAMA Cardiol. 2021 Feb 1;6(2):139-147.

Sex, Permanent Drug Discontinuation, and Study Retention in Clinical Trials: Insights From the TIMI trials. Circulation. 2021 Feb 16;143(7):685-695.

Efficacy and Safety of Long-Term Evolocumab Use Among Asian Subjects – A Subgroup Analysis of the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) Trial. Circ J. 2021 Oct 25;85(11):2063-2070.

Combining High-Sensitivity Troponin With the American Heart Association/American College of Cardiology Cholesterol Guidelines to Guide Evolocumab Therapy. Circulation. 2021 Jul 20;144(3):249-251. 

Cardiovascular Benefit of Lowering LDL Cholesterol Below 40 mg/dl. Circulation. 2021 Nov 23;144(21):1732-1734.

Myocardial Infarction and Evolocumab-Reply. JAMA Cardiol. 2021 Oct 1;6(10):1222-1223.

Assessment of the Change of a Continuous Variable as a Function of its Initial Value-Reply. JAMA Cardiol. 2021 Nov 1;6(11):1342-1343.

Association of Apolipoprotein B-Containing Lipoproteins and Risk of Myocardial Infarction in Individuals With and Without Atherosclerosis: Distinguishing Between Particle Concentration, Type, and Content. JAMA Cardiol. 2022 Mar 1;7(3):250-256.

Can machine learning bring cardiovascular risk assessment to the next level? A methodological study using FOURIER trial data. European Heart Journal – Digital Health, Volume 3, Issue 1, March 2022, Pages 38–48.

Effect of evolocumab on acute arterial events across all vascular territories : results from the FOURIER trial. Eur Heart J. 2021 Dec 14;42(47):4821-4829.

Effect of Evolocumab in Patients With Prior Percutaneous Coronary Intervention. Circ Cardiovasc Interv. 2022 Mar;15(3):e011382. 

No association between APOE genotype and lipid lowering with cognitive function in a randomized controlled trial of evolocumab. PLoS One. 2022 Apr 11;17(4):e0266615.

A polygenic risk score predicts atrial fibrillation in cardiovascular disease. Eur Heart J. 2023 Jan 14;44(3):221-231.

Biomarker Prediction of Complex Coronary Revascularization Procedures in the FOURIER Trial. J Am Coll Cardiol. 2022 Aug 30;80(9):887-897.

Growth differentiation factor 15 and cardiovascular risk: individual patient meta-analysis. Eur Heart J. Eur Heart J . 2023 Jan 21;44(4):293-300.

Assessment of Atherothrombotic Risk in Patients With Type 2 Diabetes Mellitus. JACC. 2023;25:2391-2402.

Risk Assessment of Kidney Disease Progression and Efficacy of SGLT2 Inhibition in Patients With Type 2 Diabetes. Diabetes Care. 2023 Aug 9:dc230492. doi: 10.2337/dc23-0492.