Nearly all ACS patients reach LDL-c goal when PCSK9i is added to optimal statin therapy

Achievement of ESC/EAS LDL-C treatment goals after an acute coronary syndrome with statin and alirocumab

Literature - Landmesser U, McGinniss J, Steg G, et al. - Eur J Prev Cardiol. 2022 Jun 16;zwac107, doi: 10.1093/eurjpc/zwac107

Introduction and methods


The 2019 ESC/EAS dyslipidaemia guidelines recommend an LDL-c treatment goal of<1.4 mmol/L (and LDL-c reduction >50%) after recent acute coronary syndrome (ACS ) and <1.0 mmol/L in case of additional recurrent CV events within 2 years [1]. However, many ACS patients do not achieve these goals on statins alone. For them, combination treatment is advised.

Aim of the study

The authors examined the actual achievement of the LDL-c goal (<1.4 or <1.0 mmol/L) with the PCSK9i alirocumab and the projected goal achievement with ezetimibe in ACS patients with LDL-c ≥1.4 mmol/L despite optimal statin therapy.


This was a post-hoc analysis of the ODYSSEY OUTCOMES trial. In this multicenter, double-blind, placebo-controlled phase 3 RCT, patients with recent ACS (1–12 months prior to randomization) and hyperlipidemia despite high-intensity or maximum-tolerated statin therapy were randomly assigned (1:1 ratio) to alirocumab 75 mg subcutaneously every 2 months or placebo [2]. This subanalysis comprised 17,589 patients with LDL-c ≥1.4 mmol/L at baseline who did not receive ezetimibe treatment after randomization.


The number of patients who achieved LDL-c<1.4 mmol/L at any post-randomization time point was determined. In a subset of patients with ≥1 other CV event (f.e., MI, unstable angina, stroke, or coronary revascularization) in the 2 years preceding the qualifying ACS, the number of patients who achieved LDL-c <1.0 mmol/L at any post-randomization time point was assessed.

A simulation analysis was used to project the number of patients who would have met new guideline targets at baseline or at least once after randomization if ezetimibe had been added to their treatment (assuming 18±3% reduction of LDL-c levels).

Main results

LDL-c goal <1.4 mmol/L

  • At baseline, median LDL-c level was 2.3 mmol/L (IQR: 1.9−2.7), with 15,619 patients (88.8%) receiving high-intensity statin treatment (atorvastatin 40−80 mg/day or rosuvastatin 20−40 mg/day).
  • In the alirocumab group (n=8795), 94.6% of the patients (range: 70.8%–97.9%) achieved LDL-c <1.4 mmol/L at least once compared with 17.3% (range: 6.0%–42.6%) in the placebo group (n=8630). These ranges indicate that the percentage of patients that met this treatment goal depend on their baseline LDL-c levels: Patients with a lower baseline level more frequently met the treatment goal than those with higher baseline levels.

LDL-c goal <1.0 mmol/L

  • Of the 2236 patients with ≥1 other CV event within 2 years before the qualifying ACS, 940/1103 patients (85.2%) achieved LDL-c <1.0 mmol/L in the alirocumab group compared with 39/1109 (3.5%) in the placebo group.
  • The likelihood of achieving this treatment goal also depended on the baseline LDL-c level. Of the patients with baseline LDL-c <1.8 mmol/L, 130/138 patients (94.2%) in the alirocumab group and 12/150 (8.0%) in the placebo group met the goal. In contrast, this goal was achieved by 43/82 patients (52.4%) and 0/75 patients (0%), respectively, when the baseline LDL-c level was ≥3.9 mmol/L.

Projected goal achievement with ezetimibe

  • Of the patients not treated with ezetimibe at baseline or after randomization , 1815 (10.6%) would have achieved LDL-c<1.4 mmol/L at baseline if they had been treated with this drug and with optimal statin therapy, but none would have had an LDL-c baseline level <1.0 mmol/L.
  • In the alirocumab group, 8260/8548 patients (96.6%) would have met the LDL-c goal of <1.4 mmol/L at least once if they had been treated with optimal statin therapy and ezetimibe prior to randomization compared with 3507/8372 patients (41.9%) in the placebo group.
  • Among the 2099 patients with ≥1 other CV event within 2 years, adding ezetimibe would have resulted in 91.0% meeting the LDL-c goal of <1.0 mmol/L in the alirocumab group and 8.3% in the placebo group.


Among patients with recent ACS and LDL-c ≥1.4 mmol/L despite optimal statin therapy, addition of alirocumab resulted in 95% achieving the 2019 ESC/EAS guideline LDL-c goal of<1.4 mmol/L and 85% of those with recurrent CV events to achieving <1.0 mmol/L. If ezetimibe had been added to optimal statin therapy instead, only 11% of the patients were projected to achieve LDL-c <1.4 mmol/L. However, 97% would have met this goal if they had received triple therapy consisting of a statin, ezetimibe, and alirocumab.


1. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al.; ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41:111-88.

2. Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, et al.; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018;379:2097-107.

Find this article online at Eur J Prev Cardiol.

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