Impact of PCSK9 inhibition on coronary atheroma progression: Rationale and design of Global Assessment of Plaque Regression with a PCSK9 Antibody as Measured by Intravascular Ultrasound (GLAGOV).

Puri, Rishi; Nissen, Steven E; Somaratne, Ransi; Cho, Leslie; Kastelein, John J P; Ballantyne, Christie M; Koenig, Wolfgang; Anderson, Todd J; Yang, Jingyuan; Kassahun, Helina; Wasserman, Scott M; Scott, Robert; Borgman, Marilyn; Nicholls, Stephen J

doi:10.1016/j.ahj.2016.01.019

journal article

Dokumenttyp:: Journal Article; Article
Autor(en):: Puri, Rishi; Nissen, Steven E; Somaratne, Ransi; Cho, Leslie; Kastelein, John J P; Ballantyne, Christie M; Koenig, Wolfgang; Anderson, Todd J; Yang, Jingyuan; Kassahun, Helina; Wasserman, Scott M; Scott, Robert; Borgman, Marilyn; Nicholls, Stephen J
Titel:: Impact of PCSK9 inhibition on coronary atheroma progression: Rationale and design of Global Assessment of Plaque Regression with a PCSK9 Antibody as Measured by Intravascular Ultrasound (GLAGOV).
Abstract:: Statin-mediated low-density lipoprotein cholesterol (LDL-C) lowering fails to prevent more than half of cardiovascular events in clinical trials. Serial plaque imaging studies have highlighted the benefits of aggressive LDL-C lowering, with plaque regression evident in up to two-thirds of patients with achieved LDL-C levels <70 mg/dL. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors permit LDL-C-lowering by a further 54% to 75% in statin-treated patients. The impact of achieving very low LDL-C levels with PCSK9 inhibitors on coronary atherosclerosis has not been investigated.To test the hypothesis that incremental LDL-C lowering with the PCSK9 inhibitor, evolocumab, will result in a significantly greater change from baseline in coronary atheroma volume than placebo in subjects receiving maximally tolerated statin therapy.A phase 3, multicenter, double-blind, randomized, placebo-controlled trial evaluating the impact of evolocumab on coronary atheroma volume as assessed by serial coronary intravascular ultrasound at baseline in patients undergoing a clinically indicated coronary angiogram with angiographic evidence of coronary atheroma, and after 78 weeks of treatment. Subjects (n = 968) were randomized 1:1 into 2 groups to receive monthly either evolocumab 420 mg or placebo subcutaneous injections.The GLAGOV trial will explore whether greater degrees of plaque regression are achievable with ultrahigh-intensity LDL-C lowering after combination statin-PCSK9 inhibitor therapy. GLAGOV will provide important mechanistic, safety, and efficacy data prior to the eagerly anticipated clinical outcomes trials testing the PCSK9 inhibitor hypothesis (www.clinicaltrials.gov identifier NCT01813422).
Zeitschriftentitel:: Am Heart J
Jahr:: 2016
Band / Volume:: 176
Seitenangaben Beitrag:: 83-92
Sprache:: eng
Volltext / DOI:: doi:10.1016/j.ahj.2016.01.019
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/27264224
Print-ISSN:: 0002-8703
TUM Einrichtung:: Klinik für Herz- und Kreislauferkrankungen im Erwachsenenalter (Prof. Schunkert)
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Lehr- und Forschungskooperationen mit den Kliniken und Instituten am Deutschen Herzzentrum Klinik für Herz- und Kreislauferkrankungen im Erwachsenenalter (DHM) (Prof. Schunkert)2016