Physicians' Academy for Cardiovascular Education

PCSK9i reduces MACE regardless of number of metabolic risk factors

Metabolic risk factors and effect of alirocumab on cardiovascular events after acute coronary syndrome: a post-hoc analysis of the ODYSSEY OUTCOMES randomised controlled trial

Literature - Ostadal P, Steg PG, Poulouin Y, et al. - Lancet Diabetes Endocrinol. 2022;10:330-40. doi: 10.1016/S2213-8587(22)00043-2.

Introduction and methods


Although it has been demonstrated that high-intensity statin therapy decreases the risk of MACE in patients with metabolic syndrome and chronic coronary artery disease (CAD) or acute coronary syndrome (ACS), the residual risk in individuals with metabolic syndrome remains high [1,2].

Aim of the study

The aim of the study was to describe the association of metabolic risk factors with the risk of MACE in patients with ACS on high-intensity or maximum-tolerated statin therapy as well as assessing the effect of the PCSK9 inhibitor alirocumab according to the number of metabolic risk factors present.


This was a post-hoc analysis of the ODYSSEY OUTCOMES trial. ODYSSEY OUTCOMES was a randomized, double-blind trial comparing the efficacy and safety of alirocumab versus placebo in patients with recent ACS (in the past 1-12 months) who were treated with high-intensity or maximum tolerated statins [2]. Patients (≥40 years) with elevated levels of atherogenic lipoproteins were randomized to 75 mg alirocumab every 2 weeks (n=9462) or placebo (n=9462). Follow-up was 2.8 (IQR 2.3-3.4) years.

Metabolic risk factors were defined as blood pressure ≥130/85 mmHg or treatment with antihypertensive medication, triglyceride concentration ≥150 mg/dL, HDL-c <40 mg/dL for men and 50 mg/dL for women, fasting plasma glucose concentration ≥100 mg/dL or treatment with glucose-lowering medication and BMI ≥30 kg/m².


The primary outcome for this post-hoc analysis was composite of death from CAD, non-fatal MI, fatal or non-fatal ischemic stroke, or unstable angina requiring hospital admission.

The effect of alirocumab was compared across subgroups by number of metabolic risk factors and between groups ≥3 vs. < 3 metabolic risk factors (≥3 risk factors corresponds with the definition of metabolic syndrome). Also, an analysis excluding patients with diabetes was performed as diabetes is a strong independent risk factor for CV events.

Main results

Subgroups by number of metabolic risk factors

Analysis excluding patients with diabetes


The accumulation of metabolic risk factors was associated with a higher risk of MACE in patients with recent ACS. Alirocumab reduced MACE consistently across categories defined by the number of metabolic risk factors, but aRR increased with number of metabolic risk factors.


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Find this article online at Lancet Diabetes Endocrinol.

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