A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Impact of Evolocumab on Major Cardiovascular Events in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke
A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Impact of Evolocumab on Major Cardiovascular Events in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke
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.
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:
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:
C. Significant peripheral arterial disease meeting at least 1 of the following criteria:
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
Beverly Hills, California 90210, United States
Fort Lauderdale, Florida 33312, United States
Kingston, New York 12401, United States
Southampton, New York 11968, United States
Greenville, South Carolina 29607, United States
CABA, Buenos Aires C1023AAB, Argentina
CABA, Buenos Aires C1027AAP, Argentina
CABA, Buenos Aires C1119ACN, Argentina
CABA, Buenos Aires C1406BOA, Argentina
CABA, Buenos Aires C1407GTN, Argentina
CABA, Buenos Aires C1425AGC, Argentina
CABA, Buenos Aires C1425BNG, Argentina
CABA, Buenos Aires C1425DES, Argentina
CABA, Buenos Aires C1426ABP, Argentina
CABA, Buenos Aires C1426ABP, Argentina
Ciudad Autonoma de Buenos Aires, Buenos Aires C1012AAR, Argentina
Ciudad Autonoma de Buenos Aires, Buenos Aires C1093AAS, Argentina
Ciudad Autonoma de Buenos Aires, Buenos Aires C1428ART, Argentina
Ciudad Autonoma de Buenos Aires, Buenos Aires C1430CKE, Argentina
San Nicolás de los Arroyos, Buenos Aires B2900DMH, Argentina
Rosario, Santa Fe Province 2000, Argentina
San Miguel de Tucumán, Tucumán Province 4000, Argentina
Bentley, Western Australia 6102, Australia
Curitiba, Paraná 80230-130, Brazil
Porto Alegre, Rio Grande do Sul 90610-000, Brazil
São José do Rio Preto, São Paulo 15090-000, Brazil
São Paulo, 05403-000, Brazil
Burgas, 8000, Bulgaria
Pernik, 2300, Bulgaria
Plovdiv, 4003, Bulgaria
Sofia, 1527, Bulgaria
Sofia, 1606, Bulgaria
Veliko Tarnovo, 5002, Bulgaria
London, Ontario N6G 2M1, Canada
Saint-Jérôme, Quebec J7Z 5T3, Canada
Havirov - Mesto, 736 01, Czechia
Klatovy IV, 339 01, Czechia
Kolin III, 280 02, Czechia
Ostrava - Poruba, 708 00, Czechia
Ostrava-Dubina, 700 30, Czechia
Praha 10 - Zabehlice, 106 00, Czechia
Praha 5 - Smichov, 150 00, Czechia
Lyon Cédex 3, 69437, France
Montpellier, 34295, France
Bad Neuheim, 61231, Germany
Dresden, 01307, Germany
Frankfurt am Main, 60590, Germany
Markleeberg, 04416, Germany
Kalocsa, 6300, Hungary
Szeged, 6725, Hungary
Szeged, 6725, Hungary
Kaunas, 50009, Lithuania
Cd de Mexico, Mexico City 06700, Mexico
Culiacán, Sinaloa 80230, Mexico
Chrzanów, 32-500, Poland
Grodzisk Mazowiecki, 05-825, Poland
Kielce, 25-525, Poland
Krosno, 38-400, Poland
Ruda Śląska, 41-709, Poland
Siedlce, 08-110, Poland
Tarnów, 33-100, Poland
Wroclaw, 50-315, Poland
Matosinhos Municipality, 4464-513, Portugal
Bucharest, 022328, Romania
Barnaul, 656055, Russia
Izhevsk, 426063, Russia
Kemerovo, 650002, Russia
Kirov, 610014, Russia
Krasnodar, 350086, Russia
Moscow, 111539, Russia
Nizhny Novgorod, 603126, Russia
Saint Petersburg, 192283, Russia
Saint Petersburg, 192289, Russia
Saint Petersburg, 195112, Russia
Saint Petersburg, 199106, Russia
Sait-Petersburg, 194044, Russia
Smolensk, 214018, Russia
Tomsk, 634012, Russia
Tyumen, 625032, Russia
Yekaterinburg, 620102, Russia
Seongnam-si, Gyeonggi-do, 13620, South Korea
Suwon-si, Gyeonggi-do, 16499, South Korea
Las Palmas de Gran Canarias, Canary Islands 35010, Spain
Ivano-Frankivsk, 76018, Ukraine
Kyiv, 02232, Ukraine
Kyiv, 03680, Ukraine
Kyiv, 03680, Ukraine
Vinnytsia, 21018, Ukraine
Zaporizhzhya, 69035, Ukraine
Burton-on-Trent, DE13 0RB, United Kingdom