A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia

Simple item page
dc.contributor.authorBlom, Dirk J
dc.contributor.authorHala, Tomas
dc.contributor.authorBolognese, Michael
dc.contributor.authorLillestol, Michael J
dc.contributor.authorToth, Phillip D
dc.contributor.authorBurgess, Lesley
dc.contributor.authorCeska, Richard
dc.contributor.authorRoth, Eli
dc.contributor.authorKoren, Michael J
dc.contributor.authorBallantyne, Christie M
dc.contributor.authorMonsalvo, Maria Laura
dc.contributor.authorTsirtsonis, Kate
dc.contributor.authorKim, Jae B
dc.contributor.authorScott, Rob
dc.contributor.authorWasserman, Scott M
dc.contributor.authorStein, Evan A
dc.date.accessioned2021-10-08T07:22:53Z
dc.date.available2021-10-08T07:22:53Z
dc.date.issued2014
dc.description.abstractBACKGROUND Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/ kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in phase 2 studies. We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab. METHODS We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program. On the basis of this classification, patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily, atorvastatin at a dose of 80 mg daily, or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily, for a run-in period of 4 to 12 weeks. Patients with an LDL cholesterol level of 75 mg per deciliter (1.9 mmol per liter) or higher were then randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo every 4 weeks. The primary end point was the percent change from baseline in LDL cholesterol, as measured by means of ultracentrifugation, at week 52. RESULTS Among the 901 patients included in the primary analysis, the overall least-squares mean (±SE) reduction in LDL cholesterol from baseline in the evolocumab group, taking into account the change in the placebo group, was 57.0±2.1% (P<0.001). The mean reduction was 55.7±4.2% among patients who underwent background therapy with diet alone, 61.6±2.6% among those who received 10 mg of atorvastatin, 56.8±5.3% among those who received 80 mg of atorvastatin, and 48.5±5.2% among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe (P<0.001 for all comparisons). Evolocumab treatment also significantly reduced levels of apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein(a), and triglycerides. The most common adverse events were nasopharyngitis, upper respiratory tract infection, influenza, and back pain. CONCLUSIONS At 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of cardiovascular risks.
dc.identifier.apacitationBlom, D. J., Hala, T., Bolognese, M., Lillestol, M. J., Toth, P. D., Burgess, L., ... Stein, E. A. (2014). A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia. <i>The New England Journal of Medicine</i>, 370(19), 1809 - 1819. http://hdl.handle.net/11427/35021en_ZA
dc.identifier.chicagocitationBlom, Dirk J, Tomas Hala, Michael Bolognese, Michael J Lillestol, Phillip D Toth, Lesley Burgess, Richard Ceska, et al "A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia." <i>The New England Journal of Medicine</i> 370, 19. (2014): 1809 - 1819. http://hdl.handle.net/11427/35021en_ZA
dc.identifier.citationBlom, D.J., Hala, T., Bolognese, M., Lillestol, M.J., Toth, P.D., Burgess, L., Ceska, R. & Roth, E. et al. 2014. A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia. <i>The New England Journal of Medicine.</i> 370(19):1809 - 1819. http://hdl.handle.net/11427/35021en_ZA
dc.identifier.issn0028-4793
dc.identifier.issn1533-4406
dc.identifier.ris TY - Journal Article AU - Blom, Dirk J AU - Hala, Tomas AU - Bolognese, Michael AU - Lillestol, Michael J AU - Toth, Phillip D AU - Burgess, Lesley AU - Ceska, Richard AU - Roth, Eli AU - Koren, Michael J AU - Ballantyne, Christie M AU - Monsalvo, Maria Laura AU - Tsirtsonis, Kate AU - Kim, Jae B AU - Scott, Rob AU - Wasserman, Scott M AU - Stein, Evan A AB - BACKGROUND Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/ kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in phase 2 studies. We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab. METHODS We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program. On the basis of this classification, patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily, atorvastatin at a dose of 80 mg daily, or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily, for a run-in period of 4 to 12 weeks. Patients with an LDL cholesterol level of 75 mg per deciliter (1.9 mmol per liter) or higher were then randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo every 4 weeks. The primary end point was the percent change from baseline in LDL cholesterol, as measured by means of ultracentrifugation, at week 52. RESULTS Among the 901 patients included in the primary analysis, the overall least-squares mean (±SE) reduction in LDL cholesterol from baseline in the evolocumab group, taking into account the change in the placebo group, was 57.0±2.1% (P<0.001). The mean reduction was 55.7±4.2% among patients who underwent background therapy with diet alone, 61.6±2.6% among those who received 10 mg of atorvastatin, 56.8±5.3% among those who received 80 mg of atorvastatin, and 48.5±5.2% among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe (P<0.001 for all comparisons). Evolocumab treatment also significantly reduced levels of apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein(a), and triglycerides. The most common adverse events were nasopharyngitis, upper respiratory tract infection, influenza, and back pain. CONCLUSIONS At 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of cardiovascular risks. DA - 2014 DB - OpenUCT DP - University of Cape Town IS - 19 J1 - The New England Journal of Medicine LK - https://open.uct.ac.za PY - 2014 SM - 0028-4793 SM - 1533-4406 T1 - A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia TI - A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia UR - http://hdl.handle.net/11427/35021 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/35021
dc.identifier.vancouvercitationBlom DJ, Hala T, Bolognese M, Lillestol MJ, Toth PD, Burgess L, et al. A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia. The New England Journal of Medicine. 2014;370(19):1809 - 1819. http://hdl.handle.net/11427/35021.en_ZA
dc.publisher.departmentDepartment of Medicine
dc.publisher.facultyFaculty of Health Sciences
dc.sourceThe New England Journal of Medicine
dc.source.journalissue19
dc.source.journalvolume370
dc.source.pagination1809 - 1819
dc.source.urihttps://dx.doi.org/10.1056/NEJMoa1316222
dc.subject.otherAdult
dc.subject.otherAged
dc.subject.otherAntibodies, Monoclonal
dc.subject.otherAtorvastatin Calcium
dc.subject.otherAzetidines
dc.subject.otherCholesterol, LDL
dc.subject.otherCombined Modality Therapy
dc.subject.otherDouble-Blind Method
dc.subject.otherEzetimibe
dc.subject.otherFemale
dc.subject.otherHeptanoic Acids
dc.subject.otherHumans
dc.subject.otherHydroxymethylglutaryl-CoA Reductase Inhibitors
dc.subject.otherHyperlipidemias
dc.subject.otherLeast-Squares Analysis
dc.subject.otherMale
dc.subject.otherMiddle Aged
dc.subject.otherProprotein Convertase 9
dc.subject.otherProprotein Convertases
dc.subject.otherPyrroles
dc.subject.otherSerine Endopeptidases
dc.subject.otherAMG 145
dc.subject.otherAntibodies, Monoclonal
dc.subject.otherAzetidines
dc.titleA 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
BlomDirkJ_A_52_Week_Place_2014.pdf
Size:
535.83 KB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Journal Articles