Coronary Heart Disease (CHD)
Conditions
Keywords
High Cardiovascular Risk, No prior Myocardial Infarction stroke, >= 50 years of age (men), >= 55 years of age (women), lipid-lowering therapy
Brief summary
This study will assess the effect of lowering low-density lipoprotein cholesterol (LDL-C) with evolocumab on major cardiovascular events in adults without a prior myocardial infarction (MI) or stroke who are at high risk of a cardiovascular event.
Interventions
DRUGEvolocumab
Administered subcutaneously using an autoinjector pen.
DRUGPlacebo
Administered subcutaneously using an autoinjector pen.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Age: Adult participants ≥ 50 (men) or ≥ 55 (women) to ˂ 80 years of age (either sex) and meeting lipid criteria. * Lipid Criteria: Low-density lipoprotein cholesterol (LDL-C) ≥ 90 mg/dL (≥ 2.3 mmol/L) or non high-density lipoprotein cholesterol (non-HDL)-C ≥ 120 mg/dL (≥ 3.1 mmol/L), or apolipoprotein B ≥ 80 mg/dL (≥ 1.56 µmol/L). 3.Diagnostic evidence of at least one of the following (A-D) at screening: A.Significant coronary artery disease (CAD) meeting at least 1 of the following criteria: * History of coronary revascularization with multi-vessel coronary disease as evidenced by any of the following: 1. percutaneous coronary intervention (PCI) of 2 or more vessels, including branch arteries, 2. PCI or coronary artery bypass grafting (CABG) with residual 50% stenosis in a separate, unrevascularized vessel, or 3. multi-vessel CABG 5 years or more prior to screening. * Significant coronary disease without prior revascularization as evidenced by either a ≥70% stenosis of at least 1 coronary artery, ≥50% stenosis of 2 or more coronary arteries, or ≥50% stenosis of the left main coronary artery. * known coronary artery calcium score ≥100 in participants without a coronary artery revascularization prior to randomization. B. Significant atherosclerotic cerebrovascular disease meeting at least 1 of the following criteria: * prior transient ischemic attack with ≥50% carotid stenosis. * internal or external carotid artery stenosis of ≥70% or 2 or more ≥50% stenoses. * prior internal or external carotid artery revascularization. C. Significant peripheral arterial disease meeting at least 1 of the following criteria: * ≥50% stenosis in a limb artery. * history of abdominal aorta treatment (percutaneous and surgical) due to atherosclerotic disease. * ankle brachial index (ABI) \<0.85. D. Diabetes mellitus with at least 1 of the following: * known microvascular disease, defined by diabetic nephropathy or treated retinopathy. Diabetic nephropathy defined as persistent microalbuminuria (urinary albumin to creatinine ratio ≥30mg/g) and/or persistent estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m\^2 that is not reversible due to an acute illness. * chronic daily treatment with an intermediate or long-acting insulin. * diabetes diagnosis ≥10 years ago. •At least 1 of the following 1 high-risk criteria (most recent lab values within 6 months prior to screening, as applicable): * Polyvascular disease, defined as coronary, carotid, or peripheral artery stenosis ≥50% in a second distinct vascular location in a participant with coronary, cerebral or peripheral arterial disease (A, B, or C above). * Presence of either diabetes mellitus or metabolic syndrome in a participant with coronary, cerebral, or peripheral artery disease (A, B, or C above). * At least 1 coronary, carotid, or peripheral artery residual stenosis of ≥50% in a participant with diabetes meeting inclusion criterion (D above). * LDL-C ≥130 mg/dL (≥3.36 mmol/L), OR non-HDL-C ≥160 mg/dL (≥4.14 mmol/L), OR apolipoprotein B ≥120 mg/dL (2.3 µmol/L) if available. * Lipoprotein (a) \>125 nmol/L (50 mg/dL). * Known familial hypercholesterolemia. * Family history of premature coronary artery disease defined as an MI or CABG in the participant's father or brother at age \<55 years or an MI or CABG in the participant's mother or sister at age \<60 years. * High sensitive c-reactive protein (hsCRP) ≥3.0 mg/L in the absence of an acute illness. * Current tobacco use. -≥65 years of age. * Menopause before 40 years of age. * eGFR 15 to \<45 mL/min/1.73 m\^2. * Coronary artery calcification score ≥300 in a participant without a coronary revascularization prior to randomization.
Exclusion criteria
* MI or stroke prior to randomization. * CABG ˂ 3 months prior to screening. * eGFR ˂ 15 mL/min/1.73 m\^2. * Uncontrolled or recurrent ventricular tachycardia in the absence of an implantable-cardioverter defibrillator. * Atrial fibrillation or atrial flutter not on anticoagulation therapy (vitamin K antagonist, heparin, low molecular weight heparin, fondaparinux,or non-Vitamin K antagonist oral anticoagulant). * Triglycerides ≥ 500 mg/dL (5.7 mmol/L) measured up to 3 months prior to screening. The most recent results must be used. * Last measured left-ventricular ejection fraction ˂ 30% or New York Heart Association (NYHA) Functional Class III/IV. * Planned arterial revascularization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Coronary Heart Disease (CHD) Death, Myocardial Infarction (MI), or Ischemic Stroke, Whichever Occurred First | From enrollment to last confirmed survival status date; median (min, max) time on trial was 55.2 (0.0, 72.7) months | All deaths and individual components were adjudicated by an independent external clinical events committee (CEC), using standardized definitions. The number of participants who experienced CHD death, MI, or ischemic stroke, whichever occurred first, among participants at high cardiovascular risk without prior MI or stroke and were receiving optimized lipid lowering therapy was analyzed. |
| Number of Participants Who Experienced CHD Death, MI, Ischemic Stroke, or Any Ischemia-driven Arterial Revascularization, Whichever Occurred First | From enrollment to last confirmed survival status date; median (min, max) time on trial was 55.2 (0.0, 72.7) months | All deaths and individual components were adjudicated by an independent external CEC, using standardized definitions. The number of participants who experienced CHD death, MI, ischemic stroke, or any ischemia-driven arterial revascularization, whichever occurred first, among participants at high cardiovascular risk without prior MI or stroke and were receiving optimized lipid lowering therapy was analyzed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced MI, Ischemic Stroke, or Any Ischemia-driven Arterial Revascularization | From enrollment to last confirmed survival status date; median (min, max) time on trial was 55.2 (0.0, 72.7) months | All deaths and individual components were adjudicated by an independent external CEC, using standardized definitions. The number of participants who experienced MI, ischemic stroke, or any ischemia-driven arterial revascularization, among participants at high cardiovascular risk without prior MI or stroke and were receiving optimized lipid lowering therapy was analyzed. |
| Number of Participants Who Experienced CHD Death, MI, or Any Ischemia-driven Arterial Revascularization | From enrollment to last confirmed survival status date; median (min, max) time on trial was 55.2 (0.0, 72.7) months | All deaths and individual components were adjudicated by an independent external CEC, using standardized definitions. The number of participants who experienced CHD death, MI, or any ischemia-driven arterial revascularization, among participants at high cardiovascular risk without prior MI or stroke and were receiving optimized lipid lowering therapy was analyzed. |
| Number of Participants Who Experienced Cardiovascular Death, MI, or Ischemic Stroke | From enrollment to last confirmed survival status date; median (min, max) time on trial was 55.2 (0.0, 72.7) months | All deaths and individual components were adjudicated by an independent external CEC, using standardized definitions. The number of participants who experienced cardiovascular death, MI, or ischemic stroke, among participants at high cardiovascular risk without prior MI or stroke and were receiving optimized lipid lowering therapy was analyzed. |
| Number of Participants Who Experienced CHD Death or MI | From enrollment to last confirmed survival status date; median (min, max) time on trial was 55.2 (0.0, 72.7) months | All deaths and individual components were adjudicated by an independent external CEC, using standardized definitions. The number of participants who experienced CHD death or MI, among participants at high cardiovascular risk without prior MI or stroke and were receiving optimized lipid lowering therapy was analyzed. |
| Number of Participants Who Experienced MI | From enrollment to last confirmed survival status date; median (min, max) time on trial was 55.2 (0.0, 72.7) months | All deaths and individual components were adjudicated by an independent external CEC, using standardized definitions. The number of participants who experienced MI, among participants at high cardiovascular risk without prior MI or stroke and were receiving optimized lipid lowering therapy was analyzed. |
| Number of Participants Who Experienced Any Ischemia-driven Arterial Revascularization | From enrollment to last confirmed survival status date; median (min, max) time on trial was 55.2 (0.0, 72.7) months | All deaths and individual components were adjudicated by an independent external CEC, using standardized definitions. The number of participants who experienced ischemia-driven arterial revascularization, among participants at high cardiovascular risk without prior MI or stroke and were receiving optimized lipid lowering therapy was analyzed. |
| Number of Participants Who Experienced CHD Death | From enrollment to last confirmed survival status date; median (min, max) time on trial was 55.2 (0.0, 72.7) months | All deaths and individual components were adjudicated by an independent external CEC, using standardized definitions. The number of participants who experienced CHD death, among participants at high cardiovascular risk without prior MI or stroke and were receiving optimized lipid lowering therapy was analyzed. |
| Number of Participants Who Experienced Cardiovascular Death | From enrollment to last confirmed survival status date; median (min, max) time on trial was 55.2 (0.0, 72.7) months | All deaths and individual components were adjudicated by an independent external CEC, using standardized definitions. The number of participants who experienced cardiovascular death, among participants at high cardiovascular risk without prior MI or stroke and were receiving optimized lipid lowering therapy was analyzed. |
| Number of Participants Who Died Due to Any Cause | From enrollment to last confirmed survival status date; median (min, max) time on trial was 55.2 (0.0, 72.7) months | All deaths and individual components were adjudicated by an independent external CEC, using standardized definitions. The number of participants who died due to any cause, among participants at high cardiovascular risk without prior MI or stroke and were receiving optimized lipid lowering therapy was analyzed. |
| Number of Participants Who Experienced Ischemic Stroke | From enrollment to last confirmed survival status date; median (min, max) time on trial was 55.2 (0.0, 72.7) months | All deaths and individual components were adjudicated by an independent external CEC, using standardized definitions. The number of participants who experienced ischemic stroke, among participants at high cardiovascular risk without prior MI or stroke and were receiving optimized lipid lowering therapy was analyzed. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Italy, Latvia, Lithuania, Mexico, Netherlands, Poland, Portugal, Romania, Russia, Slovakia, South Korea, Spain, Sweden, Taiwan, Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORMD
Amgen
Participant flow
Recruitment details
Participants were enrolled at 745 research centers in North America, Europe, Asia Pacific, and Latin America between June 2019 and July 2025.
Pre-assignment details
Participants were randomized in a 1:1 ratio to receive either evolocumab 140 mg subcutaneously (SC) or placebo every two weeks (Q2W) via self-administration for a duration of approximately 6 years. A total of 12,301 participants were enrolled; however, data from 44 participants were excluded from all results analyses. Participant Flow data are therefore presented for a total of 12,257 participants in Full analysis set (FAS).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 65.3 years STANDARD_DEVIATION 6.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1017 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5110 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 53 Participants |
| Race (NIH/OMB) Asian | 488 Participants |
| Race (NIH/OMB) Black or African American | 115 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 30 Participants |
| Race (NIH/OMB) White | 11401 Participants |
| Sex: Female, Male Female | 5214 Participants |
| Sex: Female, Male Male | 3533 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 539 / 6,128 | 434 / 6,129 |
| other Total, other adverse events | 35 / 6,122 | 55 / 6,125 |
| serious Total, serious adverse events | 1,772 / 6,122 | 1,726 / 6,125 |
Outcome results
None listed