Author + information
- Received July 25, 2019
- Revision received August 9, 2019
- Accepted August 12, 2019
- Published online August 31, 2019.
- Konstantinos C. Koskinas, MD, MSc1,
- Stephan Windecker, MD1,∗ (, )@unibern,
- Giovanni Pedrazzini, MD2,
- Christian Mueller, MD3,
- Stéphane Cook, MD4,
- Christian M. Matter, MD5,
- Olivier Muller, MD6,
- Jonas Häner, MD1,
- Baris Gencer, MD7,
- Carmela Crljenica, MD2,
- Poorya Amini, PhD8,
- Olga Deckarm, MD1,
- Juan F. Iglesias, MD7,
- Lorenz Räber, MD, PhD1,
- Dik Heg, PhD8 and
- François Mach, MD7
- 1Department of Cardiology, Bern University Hospital, Inselspital, University of Bern, Switzerland
- 2Cardiocentro, Lugano, Switzerland
- 3Department of Cardiology, University Hospital Basel, Basel, Switzerland
- 4Department of Cardiology, Fribourg Hospital and University, Fribourg, Switzerland
- 5Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland
- 6Service of Cardiology, Lausanne University Hospital, Lausanne, Switzerland
- 7Department of Cardiology, Geneva University Hospital, Geneva, Switzerland
- 8CTU Bern, University of Bern, Bern, Switzerland
- ↵∗Address for correspondence: Stephan Windecker, MD Professor and Chairman Department of Cardiology Bern University Hospital – INSELSPITAL University of Bern 3010 Bern, Switzerland Tel: +41 31 632 4497 Fax: +41 31 632 4771.
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.
Disclosures: KCK has received consulting fees from Amgen and Sanofi. SW reports grants from Amgen Inc., Abbott, Bayer AG, Biotronik, Boston Scientific, Bristol Meyers Squibb, Edwards Lifesciences, Medtronic, Sinomed, and Polares. CM reports grants and personal fees from Sanofi and personal fees from Amgen. CMM reports research support from Amgen. JH received travel grants from Bayer. JFI received grants and personal fees from Biotronik, Philips Volcano, and Astra Zeneca, personal fees from Terumo, Medtronic, and Cardinal Health. LR received grants and personal fees from Abbott; personal fees from Amgen, AstraZeneca, Sanofi and CSL Behring; grants from Boston Scientific, Biotronik, Heartflow, Sanofi, and Regeneron. The other authors have nothing to disclose.
Funding: This work was supported by Amgen.
- Received July 25, 2019.
- Revision received August 9, 2019.
- Accepted August 12, 2019.
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