In-hospital initiation of PCSK9 inhibitor after ACS helps achieve LDL-c target at 8 weeks

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

Literature - Koskinas KC, Windecker S, Pedrazzini G et al. - J Am Coll Cardiol. 2019 DOI: 10.1016/j.jacc.2019.08.010

Introduction and methods

Risk of recurrent events in patients with acute coronary syndromes (ACS) is particularly high early after the index event [1]. Early, in-hospital initiation of high-intensity statin treatment lowers the occurrence of early events. While statins have additional favorable effects that may play a role in this risk reduction in the acute period after ACS [2], the benefit is thought to be at least partly mediated by the reduction of LDL-related risk.

Statins have a delayed onset of action. Many ACS patients fail to attain treatment targets with intensive statin therapy alone [3]. Thus, rapid and more potent lowering of LDL-c might be of potential therapeutic benefit in these patients.

PCSK9 antibodies have been demonstrated to rapidly and effectively lower LDL-c levels. Evolocumab reduced major CV events in the context of secondary prevention [4]. Evolocumab has been evaluated from several months up to 11 years following a myocardial infarction (MI) [5], but PCSK9 antibody treatment has not been evaluated in the very high-risk, acute (within days) phase of ACS.

Thus, a randomized, placebo-controlled trial was conducted to assess evolocumab administered in-hospital in patients presenting with ACS, compared with high-intensity statin alone. This EVOPACS study was investigator-initiated. Patients not at guideline-recommended targets despite prior high-intensity statin therapy, or who were projected not to attain these targets under newly-initiated high-intensity statin therapy were included. Patients hospitalized for non-ST-elevation ACS (NSTE-ACS) with symptom onset<72 hours or ST-elevation MI (STEMI) with symptom onset <24 hours before screening were potentially eligible. 308 Eligible patients were randomly assigned (1:1) to evolocumab 420 mg every 4 weeks or placebo. Study drug at baseline was administered as early as possible (within 24 hours) following randomization. The primary efficacy endpoint was % change in calculated LDL-C from baseline to 8 weeks.

Main results

  • %Change in calculated LDL-c from baseline to week 8 differed significantly between the evolocumab (-77±15.8%, from mean 3.61 to 0.79 mmol/L) and the placebo group (-35.4±26.6%, from mean 3.42 to 2.06 mmol/L). Least-squares mean difference was -40.7% between groups (95%CI: -45.2 to -36.2).
  • Reduction in LDL-c levels was evident at 4 weeks and maintained at 8 weeks.
  • 95.7% Of patients in the evolocumab group had LDL-c <1.8 mmol/L at 8 weeks, as compared with 37.6% in the placebo group.
  • Compared to placebo, evolocumab treatment was associated with reductions of 26.5% in total cholesterol, 34.2% in apolipoprotein B, 34.6% in non-HDL-c (all P<0.001) and 20% in triglycerides (P=0.024). HDL-c was higher by 4.8% (P=0.03), and apolipoprotein A1 was not significantly altered.
  • Both treatment groups showed similar rates of patients experiencing adverse events, serious adverse events and adverse events leading to study drug discontinuation. Musculoskeletal pain was most commonly reported (5.8% vs. 2.6%, P=0.16). 7.7% vs. 7.2% of patients experienced serious adverse events in the evolocumab and placebo groups.


This is the first study evaluating therapy with a PCSK9 inhibitor initiated in-hospital in patients presenting with ACS. Evolocumab was associated with a substantially greater LDL-c reduction at 8 weeks as compared with placebo, given in addition to high-intensity statin therapy. Over 95% of patients on evolocumab achieved the LDL-c target of <1.8 mmol/L at 8 weeks.


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.

2. 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;46:1405-10.

3. Reiner Ž, De Backer G, Fras Z, et al. Lipid lowering drug therapy in patients with coronary heart disease from 24 European countries. Findings from the EUROASPIRE IV survey. Atherosclerosis 2016;246:243-50.

4. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017;376:1713-22.

5. Sabatine MS, De Ferrari GM, Giugliano RP, et al. Clinical Benefit of Evolocumab by Severity and Extent of Coronary Artery Disease. Circulation 2018;138:756-66.

Find this article online at J Am Coll Cardiol

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