Trial DesignImpact 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)
Section snippets
Effects of lowering LDL-C on atheroma: findings from early generation imaging studies
For nearly 50 years, coronary angiography had been the preferred imaging modality for diagnosing and quantifying the extent of coronary artery disease. Clinical trials using serial coronary angiography demonstrated direct relationships between achieved LDL-C levels and the progression of coronary lumen obstruction.22, 23 However, no large angiographic study demonstrated disease regression. Serial carotid B-mode ultrasonic imaging of intimal-medial thickness (cIMT) represents a noninvasive means
Study rationale and objectives
GLAGOV (NCT01813422) will evaluate the effect of evolocumab on the change in burden of coronary atherosclerosis as measured by the IVUS-derived percent atheroma volume (PAV) in subjects undergoing a clinically indicated coronary angiogram with evidence of coronary artery disease who are receiving maximally tolerated statin therapy. The primary objective of GLAGOV is to test the hypothesis that LDL-C lowering with a monthly subcutaneous injection of evolocumab 420 mg for 78 weeks will result in
Discussion
GLAGOV will be the first large-scale serial coronary imaging trial to formally test the extension of the LDL hypothesis outlined in Figure 1; that is, if achieved LDL-C levels are further reduced to approximately 40 mg/dL, even further degrees of atheroma regression than those demonstrated in SATURN might be achieved within the coronary arterial wall. GLAGOV's results will be available prior to the results of larger clinical outcomes trials testing the effects of various PCSK9 inhibitors.
Acknowledgments
No editorial or writing assistance in the preparation of this manuscript was sought.
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Dynamic natural morphologies and component changes in nonculprit subclinical atherosclerosis in patients with acute coronary syndrome at 1-year follow-up and clinical significance at 3-year follow-up
2022, AtherosclerosisCitation Excerpt :However, the proportions of the lipid and calcium components increased, and that of the fibrous component decreased significantly. Finally, previous studies have shown that inflammation plays an important role in the progression or regression of coronary plaque and fibrous cap thickness [12,42–44]. Our findings confirmed that the macrophage composition was significantly decreased in the LR group and significantly increased in the LP group along with corresponding changes in TFCT, which suggests a potential correlation between plaque regression/stabilization and inflammation control.
C-reactive protein levels and plaque regression with evolocumab: Insights from GLAGOV
2020, American Journal of Preventive CardiologyPCSK9-D374Y mediated LDL-R degradation can be functionally inhibited by EGF-A and truncated EGF-A peptides: An in vitro study
2020, AtherosclerosisCitation Excerpt :Amongst those, inhibition by fully human PCSK9 antibodies (evolocumab and alirocumab) has been studied in a wide range of patients and has shown to decrease LDL-C by ~50–70% [1]. Multiple phase 3 studies with these drugs have been already completed and the initial data show a reduction of cardiovascular endpoints [17–19]. Both alirocumab and evolocumab have been approved in 2015 for the treatment of hypercholesterolemia in the European Union and the United States.
Effect of Evolocumab on Coronary Plaque Composition
2018, Journal of the American College of CardiologyCitation Excerpt :The details of the GLAGOV (Global Assessment of Plaque Regression With a PCSK9 Antibody as Measured By Intravascular Ultrasound) trial have been described in detail previously (6,17).
Impact of out-stent plaque characteristics on vascular response after second generation drug-eluting stent implantation: iMAP-intravascular ultrasound and angioscopic study
2018, IJC Heart and VasculatureCitation Excerpt :First, it is regarded that EES has anti-inflammatory and antithrombotic effect after stent placement [14–17], and these characteristic properties of EES may be relate to reduction of underlying plaque volume. Second, it has been widely accepted that the aggressive lowering of LDL-cholesterol led to regression of coronary plaques [18]. In this study, morbidity of dyslipidemia in patients with EES implantation was significantly lower than in those with BES and R-ZES implantation (53% vs. 86 and 93%, respectively; P = 0.03).
RCT No. NCT01813422.