Evolocumab for Early Reduction of LDL-Cholesterol Levels in Patients with Acute Coronary Syndromes (EVOPACS).

Koskinas, Konstantinos C; Windecker, Stephan; Pedrazzini, Giovanni; Mueller, Christian; Cook, Stéphane; Matter, Christian M; Muller, Olivier; Häner, Jonas; Gencer, Baris; Crljenica, Carmela; Amini, Poorya; Deckarm, Olga; Iglesias, Juan F; Räber, Lorenz; Heg, Dik; Mach, François (2019). Evolocumab for Early Reduction of LDL-Cholesterol Levels in Patients with Acute Coronary Syndromes (EVOPACS). Journal of the American College of Cardiology, 74(20), pp. 2452-2462. Elsevier 10.1016/j.jacc.2019.08.010

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BACKGROUND While guidelines recommend in-hospital initiation of high-intensity statin therapy in patients with acute coronary syndromes (ACS), low-density lipoprotein cholesterol (LDL-C) target levels are frequently not attained. Evolocumab, a rapidly acting, potent LDL-C-lowering drug, has not been studied in the acute phase of ACS. OBJECTIVES To assess the feasibility, safety, and LDL-C lowering efficacy of evolocumab initiated during the in-hospital phase of ACS. METHODS We conducted an investigator-initiated, randomized, double-blind, placebo-controlled trial involving 308 patients hospitalized for ACS with elevated LDL-C levels (≥1.8 mmol/L on high-intensity statin for at least 4 weeks; ≥2.3 mmol/L on low- or moderate-intensity statin; or ≥3.2 mmol/L on no stable dose of statin). Patients were randomly assigned 1:1 to receive subcutaneous evolocumab 420mg or matching placebo, administered in-hospital and after 4 weeks, on top of atorvastatin 40mg. The primary endpoint was percentage change in calculated LDL-C from baseline to 8 weeks. RESULTS Most patients (78.2%) had not been on previous statin treatment. Mean LDL-C levels decreased from 3.61 mmol/L to 0.79 mmol/L at week 8 in the evolocumab group, and from 3.42 mmol/L to 2.06 mmol/L in the placebo group; the difference in mean percentage change from baseline was -40.7% (95% CI: -45.2 to -36.2; p<0.001). LDL-C levels <1.8 mmol/L were achieved at week 8 by 95.7% of patients in the evolocumab group vs. 37.6% in the placebo group. Adverse events and centrally adjudicated cardiovascular events were similar in both groups. CONCLUSIONS In this first randomized trial assessing a PCSK9 antibody in the very high-risk setting of ACS, evolocumab added to high-intensity statin therapy was well tolerated and resulted in substantial reduction in LDL-C levels, rendering >95% of patients within currently recommended target levels.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > CTU Bern
04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology

UniBE Contributor:

Koskinas, Konstantinos; Windecker, Stephan; Häner, Jonas; Amini, Poorya; Räber, Lorenz and Heg, Dierik Hans

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0735-1097

Publisher:

Elsevier

Language:

English

Submitter:

Beatrice Minder Wyssmann

Date Deposited:

09 Sep 2019 18:03

Last Modified:

17 Nov 2019 01:31

Publisher DOI:

10.1016/j.jacc.2019.08.010

PubMed ID:

31479722

Uncontrolled Keywords:

Evolocumab LDL-C PCSK9 inhibitor acute coronary syndrome

BORIS DOI:

10.7892/boris.133134

URI:

https://boris.unibe.ch/id/eprint/133134

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