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

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% 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.

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, 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.

CONCLUSIONS:

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).

• Authors: Rishi Puri, Steven E Nissen, Ransi Somaratne, Leslie Cho, John J P Kastelein, Christie M Ballantyne, Wolfgang Koenig, Todd J Anderson, Jingyuan Yang, Helina Kassahun, Scott M Wasserman, Robert Scott, Marilyn Borgman, Stephen J Nicholls
• Journal: American heart journal (Am Heart J) Vol. 176 Pg. 83-92 (Jun 2016) ISSN: 1097-6744 [Electronic] United States
• PMID: 27264224 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Anticholesteremic Agents
• Cholesterol, LDL
• PCSK9 Inhibitors
• PCSK9 protein, human
• Proprotein Convertase 9
• evolocumab

Topics

• Aged
• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Humanized
• Anticholesteremic Agents (administration & dosage)
• Cholesterol, LDL (blood)
• Coronary Angiography (methods)
• Coronary Artery Disease (diagnosis, drug therapy)
• Coronary Vessels (diagnostic imaging)
• Disease Progression
• Double-Blind Method
• Drug Monitoring (methods)
• Female
• Humans
• Male
• Middle Aged
• PCSK9 Inhibitors
• Plaque, Atherosclerotic (diagnostic imaging, drug therapy)
• Proprotein Convertase 9 (immunology)
• Ultrasonography, Interventional (methods)