Effect of Evolocumab on Atherogenic Lipoproteins During the Peri- and Early Postinfarction Period
Authors: Thorsten M. Leucker, Michael J. Blaha, Steven R. Jones, Michael A. Vavuranakis, Marlene S. Williams, Hong Lai, Thomas H. Schindler, Jacqueline Latina, Steven P. Schulman, Gary Gerstenblith
Journal: Circulation (2020)

◼ secondary prevention E levated low-density lipoprotein cholesterol (LDL-C) is associated with an increased risk of adverse ischemic outcomes in the early post-acute coronary syndrome (ACS) period. 1 Achieving American Heart Association/American College of Cardiology (AHA/ACC) and European Society of Cardiology (ESC) recommendations for secondary prevention in high-risk patients such as those with ACS, however, is not typically reached until 4 weeks after initiation of high-dose statins. 2 PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition offers an option for additional and more rapid LDL-C lowering during the peri-and early post-ACS period. 3he EVACS trial (Evolocumab in Acute Coronary Syndrome; ClinicalTrials.gov,Unique identifier: NCT03515304) enrolled patients with non-ST-segment-elevation myocardial infarction and troponin I of ≥5ng/mL and randomly assigned them in a 1:1 ratio to a single dose of evolocumab SQ 420 mg or matching placebo within 24 hours of presentation.We present here the LDL-C, the primary, and other atherogenic lipid outcomes, and interpret them in the clinical context by reporting the proportion of patients in each group achieving LDL-C AHA/ACC (<70 mg/dL) and ESC (<55 mg/dL for very high risk) targets at hospital discharge and 30-day follow-up.All patients received high-intensity statins unless contraindicated and were treated in accordance with current ACS guidelines.An independent Data Safety and Monitoring Board monitored the progress of the study, which was approved by the Johns Hopkins Institutional Review Board.All participants gave informed consent.Of 272 patients with type 1 non-ST-segment-elevation myocardial infarction, 57 (21%) met eligibility criteria and were randomly assigned to receive 1 dose of evolocumab SQ 420 mg or placebo.Lipid values were not an inclusion criterion and were obtained at baseline, throughout hospitalization, and at 30 days.The principal reason for exclusion was a troponin I of <5 ng/mL.Mean±SD age was 55±13 years, 26% were African American, 42% were women, 60% were on previous statin therapy, and the only significant difference was the sex distribution (male: evolocumab 22 [73%], placebo 11 [41%]; P=0.03), which was adjusted for in the analysis.Lipid-lowering therapy and intensity at baseline and changes throughout the study did not differ between the 2 groups and did not confound the study results.Results of fasting lipoproteins are presented in Fig- ure 1A.Mean±SD LDL-C levels at baseline were 91.5±35 mg/dL in the evolocumab and 89.6±41 mg/dL in the placebo group (P=0.85).We used a linear mixed-effects model with participant ID as the random effect.After adjusting for baseline LDL-C, sex, lipid-lowering therapies, time, and site, evolocumab lowered LDL-C, on average, by 28.4±4 mg/dL (χ 2 =37.8,P<0.0001).LDL-C decreased from baseline by day 1 in the evolocumab group (70.4±27 mg/dL; P<0.01 versus baseline), and was lower than that in the placebo group by day 3 (P=0.02versus placebo).The group