Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects With Elevated Risk

Overview

About this study

The primary hypothesis is that additional LDL-C lowering with Evolocumab (AMG 145) when used in addition to other treatment for dyslipidemia is well tolerated and decreases the risk of cardiovascular death, myocardial infarction, hospitalization for unstable angina, stroke, or coronary revascularization in subjects with clinically evident cardiovascular disease.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

Male or female ≥ 40 to ≤ 85 years of age
History of clinically evident cardiovascular disease at high risk for a recurrent event
Fasting LDL-C ≥ 70 mg/dL (≥ 1.8 mmol/L) ) or non-HDL-C ≥ 100 mg/dL (> 2.6 mmol/L)
Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

Exclusion Criteria:

NYHA class III or IV, or last known left ventricular ejection fraction < 30%
Uncontrolled hypertension
Uncontrolled or recurrent ventricular tachycardia
Untreated hyperthyroidism or hypothyroidism
Homozygous familial hypercholesterolemia
LDL or plasma apheresis

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location	Status
Scottsdale/Phoenix, Ariz. Mayo Clinic principal investigator F Fortuin, M.D.	Closed for enrollment

Mayo Clinic Location

Status

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

F Fortuin, M.D.

Closed for enrollment

More information

Publications

Risk of atherothrombotic events is not uniform in patients with type 2 diabetes mellitus (T2DM). Tailored risk assessment may help guide selection of pharmacotherapies for cardiovascular primary and secondary prevention. Read More on PubMed
LDL-C is the pivotal risk factor for atherosclerotic cardiovascular disease, and the benefit from LDL-C lowering is proportional to the magnitude of reduction. Clinical trials demonstrate that evolocumab reduces LDL-C levels by approximately 60% when measured at the trough of drug effect, which may underestimate cumulative LDL-C reduction. We obtained a time-averaged estimate of LDL-C lowering that included both peaks and troughs. Pooled analysis of 5 phase 2 trials included patients with hypercholesterolemia who received placebo or evolocumab (140 mg every 2 weeks [Q2W] or 420 mg monthly [QM]). Percent changes from baseline LDL-C and free serum PCSK9 were averaged across weeks 9-12. In 372 patients, time-averaged percent reduction from baseline in LDL-C with evolocumab vs placebo was 67.6% (95% CI: 63.9-71.3) with Q2W dosing and 65.0% (95% CI: 60.7-69.3) with QM dosing. The time-averaged measure yielded LDL-C reductions for evolocumab that exceeded measurements at the end of dosing intervals and may provide a better estimate of cardiovascular benefit during long-term therapy. Read More on PubMed
In October 2018, evolocumab was made available at a reduced annual list price of $5850 in the United States. This 60% reduction was aimed at improving patient access by lowering patient copays. Shortly thereafter, the 2018 American College of Cardiology/American Heart Association cholesterol management guideline was released. An updated cost-effectiveness analysis of evolocumab in the United States may be therefore of interest to payers and prescribers. Read More on PubMed
The proprotein convertase subtilisin/kexin type 9 inhibitor evolocumab has been demonstrated to reduce the composite of myocardial infarction, stroke, or cardiovascular death in patients with established atherosclerotic cardiovascular disease. To our knowledge, long-term cost-effectiveness of this therapy has not been evaluated using clinical trial efficacy data. Read More on PubMed
Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. Read More on PubMed

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