The purpose of this study is to determine if evolocumab added to regular statin therapy improves vein graft patency after coronary artery bypass graft (CABG) surgery.
Coronary artery bypass graft (CABG) surgery is a procedure in which an artery or vein from the body is grafted to a critically narrowed coronary artery to restore flow of oxygenated blood to the heart. Statins are frequently prescribed after CABG surgery in order to lower LDL cholesterol levels and reduce the chances of coronary artery obstruction recurring. Despite this preventive measure, new vein grafts do end up becoming blocked in a significant proportion of patients. Evolocumab (Repatha®) is a recently approved medication that has been shown to effectively lower LDL cholesterol levels in the blood. NEWTON-CABG is an investigator-initiated multicenter, double-blind, randomized, placebo-controlled, parallel group study of evolocumab \[140mg administered subcutaneously (SC) every two weeks (Q2W)\] added to statin therapy for 24 months postoperatively in a broad population of patients undergoing CABG surgery. Eligible subjects will be randomized to receive evolocumab or placebo within 21 days of index CABG. Prior to randomization, post-operative patients will be on moderate or high intensity statin therapy (atorvastatin 40-80mg, rosuvastatin 20-40mg or simvastatin 40mg daily unless another statin/dose or non-statin alternative is clinically justified). A CTAngiogram will be conducted at 24 months following CABG. Routine study visits will be done 3, 6, 12, 18 and 24 months post-surgery. This study is supported by Amgen Inc.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
782
REPATHA (evolocumab) is a human immunoglobulin G2 (IgG2) monoclonal antibody that has high affinity binding to Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9); it will be administered via subcutaneous injection
Placebo cartridges will contain vehicle only; placebo will be administered via subcutaneous injection.
San Francisco VA Medical Center
San Francisco, California, United States
Saphenous vein graft disease rate (VGDR)
Saphenous vein graft disease rate (VGDR) is defined as the proportion of vein grafts with significant stenosis or total occlusion (≥50%) on 64-slice (or greater) cardiac CT angiography (CTA) or clinically indicated coronary angiography.
Time frame: 24 months post CABG
The proportion of patients with at least 1 vein graft totally (100%) occluded.
Proportion of patients who have at least 1 totally (100%) occluded vein graft at 24 months post CABG.
Time frame: 24 months post CABG
The percentage of vein grafts which are totally (100%) occluded grafts.
Percentage of vein grafts that are totally (100%) occluded at 24 months post CABG.
Time frame: 24 months post CABG
Hierarchical composite of the following (each assessed by total wins for each treatment group and the win ratio):
1. time to cardiovascular death from baseline to end of study 2. time to first myocardial infarction from baseline to end of study 3. time to first coronary revascularization from baseline to end of study 4. number of vein grafts with 100% stenosis at end of study 5. number of vein grafts with 50-99% stenosis at end of study 6. number of occluded arterial grafts at end of study 7. total plaque volume at end of study a. time to cardiovascular death from baseline to end of study b. time to first myocardial infarction from baseline to end of study c. time to first coronary revascularization from baseline to end of study d. number of vein grafts with 100% stenosis at end of study e. number of vein grafts with 50-99% stenosis at end of study f. number of occluded arterial grafts at end of study g. total plaque volume at end of study
Time frame: 24 months post CABG
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