Journal article
Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events
The New England journal of medicine, Vol.372(16), pp.1500-1509
04/16/2015
DOI: 10.1056/NEJMoa1500858
PMID: 25773607
Abstract
BACKGROUND
Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in short-term studies. We conducted two extension studies to obtain longer-term data.
METHODS
In two open-label, randomized trials, we enrolled 4465 patients who had completed 1 of 12 phase 2 or 3 studies ("parent trials") of evolocumab. Regardless of study-group assignments in the parent trials, eligible patients were randomly assigned in a 2: 1 ratio to receive either evolocumab (140 mg every 2 weeks or 420 mg monthly) plus standard therapy or standard therapy alone. Patients were followed for a median of 11.1 months with assessment of lipid levels, safety, and (as a prespecified exploratory analysis) adjudicated cardiovascular events including death, myocardial infarction, unstable angina, coronary revascularization, stroke, transient ischemic attack, and heart failure. Data from the two trials were combined.
RESULTS
As compared with standard therapy alone, evolocumab reduced the level of LDL cholesterol by 61%, from a median of 120 mg per deciliter to 48 mg per deciliter (P<0.001). Most adverse events occurred with similar frequency in the two groups, although neurocognitive events were reported more frequently in the evolocumab group. The risk of adverse events, including neurocognitive events, did not vary significantly according to the achieved level of LDL cholesterol. The rate of cardiovascular events at 1 year was reduced from 2.18% in the standard-therapy group to 0.95% in the evolocumab group (hazard ratio in the evolocumab group, 0.47; 95% confidence interval, 0.28 to 0.78; P=0.003).
CONCLUSIONS
During approximately 1 year of therapy, the use of evolocumab plus standard therapy, as compared with standard therapy alone, significantly reduced LDL cholesterol levels and reduced the incidence of cardiovascular events in a prespecified but exploratory analysis.
Details
- Title: Subtitle
- Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events
- Creators
- Marc S. Sabatine - Brigham and Women's HospitalRobert P. Giugliano - Brigham and Women's HospitalStephen D. Wiviott - Brigham and Women's HospitalFrederick J. Raal - University of the WitwatersrandDirk J. Blom - University of Cape TownJennifer Robinson - University of IowaChristie M. Ballantyne - Baylor College of MedicineRansi Somaratne - Amgen (United States)Jason Legg - Amgen (United States)Scott M. Wasserman - Amgen (United States)Robert Scott - Amgen (United States)Michael J. Koren - Jacksonville Ctr Clin Res, Jacksonville, FL USAEvan A. Stein - Metab & Atherosclerosis Res Ctr, Cincinnati, OH USAOpen-Label Study of Long-Term Evaluation against LDL Cholesterol (OSLER) Investigators
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.372(16), pp.1500-1509
- DOI
- 10.1056/NEJMoa1500858
- PMID
- 25773607
- NLM abbreviation
- N Engl J Med
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Publisher
- Massachusetts Medical Soc
- Number of pages
- 10
- Grant note
- Amgen
- Language
- English
- Date published
- 04/16/2015
- Academic Unit
- Epidemiology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984363664202771
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