PCSK9i initiated within 24 hours of ACS presentation rapidly lowers LDL-c

Effect of Evolocumab on Atherogenic Lipoproteins During the Peri- and Early Postinfarction Period: A Placebo-Controlled, Randomized Trial

Literature - Leucker TM, Blaha MJ, Jones SR et al., - Circulation. 2020 Jul 28;142(4):419-421. doi: 10.1161/CIRCULATIONAHA.120.046320.

Introduction and methods

Elevated LDL-c in an early post-acute coronary syndrome (ACS) period is associated with an increased risk of adverse ischemic outcomes [1]. However, achievement of AHA/ACC and ESC recommendations for secondary prevention in high-risk patients with high-dose statins are often not reached until 4 weeks after initiation [2]. This study investigated whether PCSK9 inhibition offers more rapid LDL-c lowering during the peri- and early post-ACS period.

A total of 57 patients with type 1 non-STEMI and troponin I ≥5 ng/mL were randomized to receive either a single dose of evolocumab SQ 420 mg (n=30) or matching placebo (n=27) within 24 hours of presentation. All patients were on high-intensity statins (unless contraindicated) and were treated in accordance with ACS guidelines. Mean age was 55 (SD:13) years, 26% were African American, 42% were women and 60% were on previous statin therapy. The current publication presented outcomes on lipid levels during hospitalization and at 30-day follow-up.

Main results

  • LDL-c levels at baseline were 91.5±35 mg/dL (mean±SD) in the evolocumab group and 89.6±41 mg/dL in the placebo group (P=0.85).
  • In the evolocumab group, LDL-c decreased from baseline by day 1 (70.4±27 mg/dL, P<0.01 versus baseline) and was lower compared to the LDL-c level in the placebo group by day 3 (P=0.02 versus placebo). LDL-c continued to be lower in the evolocumab group compared with the placebo group throughout hospitalization and at 30-day follow-up (P<0.01).
  • LDL-c levels were on average 28.6 mg/dL lower in the evolocumab group compared with the placebo group at 30 days (P<0.0001). Non-HDL-c and ApoB levels were also significantly lower in the evolocumab group compared with the placebo group at hospital discharge and 30 days. No differences between groups were found for triglyceride and HDL-c levels.
  • Proportions of participants whose LDL-c levels were at or below AHA/ACC (<70 mg/dL) and ESC (<55 mg/dL for very high risk patients) targets at hospital discharge were higher in the evolocumab group compared with the placebo group (AHA/ACC targets: 80.8% vs 38.1%, ESC targets 65.4% vs. 23.8%, P=0.01 for both comparisons).
  • Number of any adverse events and serious adverse events did not differ significantly between groups.


The outcomes of this study suggest that more patients reach secondary prevention LDL-c targets during the early post-ACS period with evolocumab plus high-intensity statin therapy compared with placebo plus high-intensity statin therapy. The clinical effects of this early, aggressive lipid lowering approach are uncertain and need to be investigated in a randomized controlled trial.


1. Wiviott SD, Cannon CP, Morrow DA, Ray KK, Pfeffer MA, Braunwald E; PROVE IT-TIMI 22 Investigators. Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy. J Am Coll Cardiol. 2005;46:1411–1416. doi: 10.1016/j.jacc.2005.04.064

2. 2. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1082–e1143. doi:10.1161/CIR.0000000000000625

Find this article online at Circulation.

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