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J Am Coll Cardiol. 2019 Nov 19;74(20):2452-2462. doi: 10.1016/j.jacc.2019.08.010. Epub 2019 Aug 31.

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

Author information

Department of Cardiology, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland.
Department of Cardiology, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland. Electronic address:
Cardiocentro, Lugano, Switzerland.
Department of Cardiology, University Hospital Basel, Basel, Switzerland.
Department of Cardiology, Fribourg Hospital and University, Fribourg, Switzerland.
Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland.
Service of Cardiology, Lausanne University Hospital, Lausanne, Switzerland.
Department of Cardiology, Geneva University Hospital, Geneva, Switzerland.
CTU Bern, University of Bern, Bern, Switzerland.



Although 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.


The purpose of this study was to assess the feasibility, safety, and LDL-C-lowering efficacy of evolocumab initiated during the in-hospital phase of ACS.


The authors 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 420 mg or matching placebo, administered in-hospital and after 4 weeks, on top of atorvastatin 40 mg. The primary endpoint was percentage change in calculated LDL-C from baseline to 8 weeks.


Most patients (78.2%) had not been on previous statin treatment. Mean LDL-C levels decreased from 3.61 to 0.79 mmol/l at week 8 in the evolocumab group, and from 3.42 to 2.06 mmol/l in the placebo group; the difference in mean percentage change from baseline was -40.7% (95% confidence interval: -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 versus 37.6% in the placebo group. Adverse events and centrally adjudicated cardiovascular events were similar in both groups.


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. (EVOlocumab for Early Reduction of LDL-cholesterol Levels in Patients With Acute Coronary Syndromes [EVOPACS]; NCT03287609).


LDL-C; PCSK9 inhibitor; acute coronary syndrome; evolocumab


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