Evolocumab for Early Reduction of LDL Cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS)
Key result
In-hospital evolocumab for ACS lowers LDL-C by ~41% at 8 weeks versus placebo.
- Difference -40.7%
- 95% CI -45.2 to -36.2
- P<0.001
- n=308
Why the study?
Target LDL-C levels are frequently not attained with in-hospital high-intensity statin therapy after ACS, and evolocumab had not been studied during the acute phase.
Does subcutaneous evolocumab 420 mg reduce LDL-C levels in patients hospitalized for acute coronary syndromes with elevated LDL-C?
Study Design
Type
RCT (n=308)
Blinding
Double-blind
Randomization
1:1
Structured PICO
Does subcutaneous evolocumab 420 mg reduce LDL-C levels in patients hospitalized for acute coronary syndromes with elevated LDL-C?
P
Population
308 patients hospitalized for acute coronary syndromes (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).
I
Intervention
Subcutaneous evolocumab 420 mg administered in-hospital and after 4 weeks, on top of atorvastatin 40 mg.
C
Comparator
Matching placebo administered in-hospital and after 4 weeks, on top of atorvastatin 40 mg.
O
Outcome
Percentage change in calculated LDL-C from baseline to 8 weeks.surrogate
Main Result
Effect estimate: Difference -40.7% (95% CI -45.2 to -36.2)
p-value: p=< 0.001
Evolocumab initiated during the in-hospital phase of ACS on top of high-intensity statin therapy safely and significantly reduced LDL-C levels, allowing >95% of patients to achieve recommended targets at 8 weeks.
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The study met its primary and secondary endpoints. What we learned from this study is that starting evolocumab very early, in hospital, in patients presenting with ACS appears to be safe and allows rapid achievement of recommended LDL targets in the vast majority — more than 90% of patients. This was achieved by only 10% of patients who were treated with statin alone, ie, with the current paradigm of lipid management in this setting.”
“The clinical impact of very early LDL cholesterol-lowering with evolocumab initiated in the acute setting of ACS warrants further investigation in a dedicated cardiovascular outcomes trial.”
“A large proportion of the patients were STEMI patients, where it would be awfully hard to administer prior to PCI, but it was at least done within 24 hours. That is very early, much earlier than any other trials.”
Implication
Supports in-hospital evolocumab to achieve LDL-C targets in ACS; extends early PCSK9i evidence but leaves clinical outcomes unproven.
Abstract
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.
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Cite This Study
Koskinas et al. (2019) conducted an RCT in Acute Coronary Syndromes (n=308). Evolocumab vs. Placebo was evaluated on Percentage change in calculated LDL-C from baseline to 8 weeks (Difference -40.7%, 95% CI -45.2 to -36.2, p=< 0.001). Evolocumab initiated in-hospital for acute coronary syndromes reduced LDL-C levels at 8 weeks compared to placebo.