Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2018 Dec;41(12):1513-1520.
doi: 10.1002/clc.23112. Epub 2018 Nov 26.

Design of the randomized, placebo-controlled evolocumab for early reduction of LDL-cholesterol levels in patients with acute coronary syndromes (EVOPACS) trial

Konstantinos C Koskinas  1 , Stephan Windecker  1 , Aliki Buhayer  2 , Baris Gencer  3 , Giovanni Pedrazzini  4 , Christian Mueller  5 , Stephan Cook  6 , Olivier Muller  7 , Christian M Matter  8 , Lorenz Räber  1 , Dik Heg  9 , François Mach  3 ; EVOPACS Investigators
Affiliations
Randomized Controlled Trial

Design of the randomized, placebo-controlled evolocumab for early reduction of LDL-cholesterol levels in patients with acute coronary syndromes (EVOPACS) trial

Konstantinos C Koskinas et al. Clin Cardiol. 2018 Dec.

Abstract

Statins lower low-density lipoprotein cholesterol (LDL-C) and improve clinical outcomes in patients with atherosclerotic cardiovascular disease (CVD). Patients with acute coronary syndromes (ACS) often do not achieve LDL-C targets despite potent statin treatment, and have a particularly high risk of early recurrent events. Evolocumab, a proprotein convertase subtilisin/kexin type (PCSK9)-inhibitor resulting in rapid, marked LDL-C reduction, has been studied in hypercholesterolemic subjects without CVD and stabilized patients with CVD; the feasibility, safety, and efficacy of this treatment initiated in the acute phase of ACS remain unknown. We report the design of evolocumab for early reduction of LDL-cholesterol levels in patients with ACS (EVOPACS), a phase-3, multicenter, randomized, double-blind, placebo-controlled trial to assess the feasibility, safety, and LDL-C-lowering efficacy of evolocumab on top of atorvastatin 40 mg in patients with ACS. The primary endpoint is percent change in LDL-C from baseline to 8 weeks. Secondary endpoints are adverse events and serious adverse events. Against a background of beneficial cardiovascular effects of statins beyond LDL-C lowering and in view of preclinical evidence of similar effects of PCSK9 inhibition, the study will also address a variety of exploratory endpoints including the change in C-reactive protein and other inflammatory biomarkers; platelet reactivity; and occurrence of contrast-induced acute kidney injury and myocardial injury in patients undergoing cardiac catheterization. An intracoronary imaging sub-study will investigate the change from baseline in the lipid core burden index in non-culprit lesions, as assessed by serial near-infrared spectroscopy. Recruitment began in January 2018 and enrollment of 308 patients is planned.

Keywords: PCSK9 inhibitor; acute coronary syndrome; lipidology.

PubMed Disclaimer

Conflict of interest statement

F.M. has received (through the Geneva University Hospital) research grants from Amgen, Sanofi, and MSD for his work in the lipid field. S.W. reports research grants to the institution from Abbott, Amgen, Bayer, Boston Scientific, Biotronik, Medtronic, Edwards Lifesciences, St Jude, Terumo. C.M. has received research grants to institution from Abbott, Beckman Coulter, Biomerieux, Brahms, Roche, Siemens, Singulex, Sphingotec, and speakers/consulting honoraria from Amgen, Astra Zeneca, Boehringer Ingelheim, Duke Research Institute, Roche, Sanofi, Siemens, and Singulex. L.R. received research grants from Sanofi/Regeneron and speaker fees from Sanofi/Regeneron and Amgen. The other authors have no conflict of interest to declare.

Figures

Figure 1
Figure 1
Study design for EVOPACS
Figure 2
Figure 2
Timing of patient enrollment following the index acute coronary event in EVOPACS (red dotted line) vs the FOURIER and ODYSSEY OUTCOMES trials. ACS indicates acute coronary syndrome; CAD, coronary artery disease; and MI, myocardial infarction
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Roffi M, Patrono C, Collet JP, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST‐segment elevation: task force for the management of acute coronary syndromes in patients presenting without persistent ST‐segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37:267‐315. - PubMed
    1. Koskinas KC, Siontis GCM, Piccolo R, et al. Effect of statins and non‐statin LDL‐lowering medications on cardiovascular outcomes in secondary prevention: a meta‐analysis of randomized trials. Eur Heart J. 2018;39:1172‐1180. - PubMed
    1. Ray KK, Cannon CP, McCabe CH, et al. Early and late benefits of high‐dose atorvastatin in patients with acute coronary syndromes. Results from the PROVE IT‐TIMI 22 trial. J Am Coll Cardiol. 2005;46:1405‐1410. - PubMed
    1. Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes. JAMA. 2001;285:1711‐1718. - PubMed
    1. Berwanger O, Santucci EV, de Barros E, et al. Effect of loading dose of atorvastatin prior to planned percutaneous coronary intervention on major adverse cardiovascular events in acute coronary syndrome: the SECURE‐PCI randomized clinical trial. JAMA. 2018;319:1331‐1340. - PMC - PubMed

Publication types

MeSH terms

Grants and funding