Addition of Evolocumab to Statin Therapy May Reduce LDL-C in Patients With ACS

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In patients with acute coronary syndrome, the early in-hospital addition of evolocumab to high-dose statin therapy was found to be safe, well tolerated, and efficacious in reducing low-density lipoprotein cholesterol levels.

In patients with acute coronary syndrome (ACS), the early in-hospital addition of evolocumab to high-dose statin therapy was found to be safe, well tolerated, and efficacious in reducing low-density lipoprotein cholesterol (LDL-C) levels, according to study results published in the Journal of the American College of Cardiology.

Although current recommendations for individuals with ACS call for initiation of in-hospital high-intensity statin therapy to reduce cardiovascular morbidity and mortality, LDL-C target levels are infrequently met. The addition of evolocumab — a proprotein convertase subtilisin/kexin type 9 monoclonal antibody that has been shown to rapidly and potently reduce LDL-C levels — to atorvastatin has not been evaluated during the acute phase of ACS.

The EVOlocumab for Early Reduction of LDL-cholesterol Levels in Patients with Acute Coronary Syndromes (EVOPACS) study ( identifier: NCT03287609) was a multicenter, phase 3, parallel-group, prospective, randomized, double-blind, placebo-controlled trial in which 308 participants (mean age, 60.8 years; 81.5% men) were enrolled between January 2018 and March 2019. Participants had elevated LDL-C levels (ie, ≥1.8 mmol/L on high-dose statin therapy for ≥4 weeks, ≥2.3 mmol/L on moderate-intensity statin therapy, or ≥3.2 mmol/L without stable statin therapy) and were hospitalized for ACS.

All participants received atorvastatin 40 mg daily and were randomly assigned to receive evolocumab 420 mg subcutaneously (n=155; mean age, 60.5 years; 82.6% men) at baseline and at 4 weeks, or matching placebo (n=153; mean age, 61.0 years; 80.4% men). Follow-up occurred at 4 and 8 weeks, and the study’s primary outcome was the percentage change from baseline to 8 weeks in LDL-C levels. Secondary outcomes included adverse events (AEs) and serious AEs (SAEs) across 8 weeks. An intention-to-treat analysis was conducted using an adjusted linear mixed effects model.

The majority of patients (78.2%) were not on a stable statin regimen at baseline; 76.3% of patients had never received a statin drug. Mean LDL-C levels were reduced from 3.61 mmol/L at baseline to 0.79 mmol/L at 8 weeks in those who received evolocumab. Levels were reduced from 3.42 mmol/L at baseline to 2.06 mmol/L at 8 weeks in the placebo group. Evolocumab was found to be more effective at lowering LDL-C compared with placebo, with a between-group difference in mean percentage change from baseline of -40.7% (95% CI, -45.2% to -36.2%; P <.001). After 8 weeks, an LDL-C target level of <1.8 mmol/L was reached by 95.7% and 37.6% of patients in the evolocumab and placebo groups, respectively.

The rates of AEs were comparable in the 2 groups, with musculoskeletal pain being most common and occurring in 5.8% and 2.6% of participants in the evolocumab and placebo groups, respectively (P =.16). In the evolocumab and placebo groups, 7.7% and 7.2% of patients reported SAEs, respectively, with 1.3% and 2.0%, respectively, reporting AEs leading to drug discontinuation. Two fatalities, both in the evolocumab group, were deemed unrelated to the study drug.

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Study limitations include the inability to analyze the primary outcome in 10% of patients, the inability to examine early evolocumab effects (ie, during the first 4 weeks), and a small sample size.

“[L]arger and longer-term studies should further investigate evolocumab in the acute ACS setting, also assessing potential effects on clinical outcomes,” noted the study authors.

Funding and Conflicts of Interest Disclosures:

This work was supported by Amgen.

Please see original article for conflict of interest declarations.


Koskinas KC, Windecker S, Pedrazzini G, et al. Evolocumab for early reduction of LDL cholesterol levels in patients with acute coronary syndromes (EVOPACS). J Am Coll Cardiol. 2019;74(20):2452-2462.