Author + information
- Received July 25, 2019
- Revision received August 9, 2019
- Accepted August 12, 2019
- Published online November 11, 2019.
- Konstantinos C. Koskinas, MD, MSca,
- Stephan Windecker, MDa,∗ (, )@unibern,
- Giovanni Pedrazzini, MDb,
- Christian Mueller, MDc,
- Stéphane Cook, MDd,
- Christian M. Matter, MDe,
- Olivier Muller, MDf,
- Jonas Häner, MDa,
- Baris Gencer, MDg,
- Carmela Crljenica, MDb,
- Poorya Amini, PhDh,
- Olga Deckarm, MDa,
- Juan F. Iglesias, MDg,
- Lorenz Räber, MD, PhDa,
- Dik Heg, PhDh and
- François Mach, MDg
- aDepartment of Cardiology, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland
- bCardiocentro, Lugano, Switzerland
- cDepartment of Cardiology, University Hospital Basel, Basel, Switzerland
- dDepartment of Cardiology, Fribourg Hospital and University, Fribourg, Switzerland
- eDepartment of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland
- fService of Cardiology, Lausanne University Hospital, Lausanne, Switzerland
- gDepartment of Cardiology, Geneva University Hospital, Geneva, Switzerland
- hCTU Bern, University of Bern, Bern, Switzerland
- ↵∗Address for correspondence:
Dr. Stephan Windecker, Department of Cardiology, Bern University Hospital–INSELSPITAL, University of Bern, 3010 Bern, Switzerland.
Background 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.
Objectives 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.
Methods 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.
Results 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.
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. (EVOlocumab for Early Reduction of LDL-cholesterol Levels in Patients With Acute Coronary Syndromes [EVOPACS]; NCT03287609)
This work was supported by Amgen. Dr. Koskinas has received consulting fees from Amgen and Sanofi. Dr. Windecker has received grants from Amgen, Abbott, Bayer AG, Biotronik, Boston Scientific, Bristol-Myers Squibb, CSL Behring, Edwards Lifesciences, Medtronic, Sinomed, and Polares. Dr. Mueller has received grants and personal fees from Sanofi; and has received personal fees from Amgen. Dr. Matter has received research support from Amgen. Dr. Häner has received travel grants from Bayer. Dr. Iglesias has received grants and personal fees from Biotronik, Philips Volcano, and AstraZeneca; and has received personal fees from Terumo, Medtronic, and Cardinal Health. Dr. Räber has received grants and personal fees from Abbott; has received personal fees from Amgen, AstraZeneca, Sanofi, and CSL Behring; and has received grants from Boston Scientific, Biotronik, Heartflow, Sanofi, and Regeneron.
- Received July 25, 2019.
- Revision received August 9, 2019.
- Accepted August 12, 2019.
- 2019 American College of Cardiology Foundation
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