Physicians' Academy for Cardiovascular Education

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


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.


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Find this article online at J Am Coll Cardiol

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