Details

Autor(en) / Beteiligte

• Puri, Rishi, MBBS, PhD
• Nissen, Steven E., MD
• Somaratne, Ransi, MD
• Cho, Leslie, MD
• Kastelein, John J.P., MD, PhD
• Ballantyne, Christie M., MD
• Koenig, Wolfgang, MD, PhD
• Anderson, Todd J., MD
• Yang, Jingyuan, PhD
• Kassahun, Hellina, MD
• Wasserman, Scott M., MD
• Scott, Robert, MD
• Borgman, Marilyn, RN
• Nicholls, Stephen J., MBBS, PhD

Titel

Impact of PCSK9 Inhibition on Coronary Atheroma Progression: Rationale and Design of GLAGOV (Global Assessment of Plaque Regression with a PCSK9 Antibody as Measured by Intravascular Ultrasound)

Ist Teil von

• The American heart journal, 2015

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Abstract Background 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 54-75% in statin-treated patients. The impact of achieving very low LDL-C levels with PCSK9 inhibitors on coronary atherosclerosis has not been investigated. Aims 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. Methods A phase 3, multi-center, 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 following 78-weeks of treatment. Subjects (n=968) were randomized 1:1 into 2 groups to either receive monthly evolocumab 420 mg or placebo subcutaneous injections. Conclusions The GLAGOV (Global Assessment of Plaque Regression with a PCSK9 Antibody as Measured by Intravascular Ultrasound) trial will explore whether greater degrees of plaque regression are achievable with ultra-high-intensity LDL-C lowering following combination statin-PCSK9 inhibitor therapy. GLAGOV will provide important mechanistic, safety and efficacy data prior the eagerly anticipated clinical outcomes trials testing the PCSK9 inhibitor hypothesis ( www.clinicaltrials.gov identifier NCT01813422).