For a study, researchers sought to investigate the impact of the PCSK9 inhibitor alirocumab against placebo on major adverse cardiovascular events (MACE) based on baseline metabolic risk variables. The ODYSSEY OUTCOMES experiment, a multicentre, double-blind, randomized controlled trial conducted in 1,315 hospitals and outpatient clinics in 57 countries, was subjected to a post-hoc analysis. Patients aged 40 and over who had recently experienced an acute coronary syndrome (within the previous 1–12 months) and had higher levels of atherogenic lipoproteins despite taking a high-intensity or maximum-tolerated statin were eligible to participate. Patients were randomly randomized (1:1) to 75 mg alirocumab by subcutaneous injection every 2 weeks, or a matching placebo commencing 1–12 months after acute coronary syndrome and monitored for 2.8 years (IQR 2.3–3.4). The group assignment and treatment dose modification were kept a secret from the patients and investigators. The primary outcome was death due to coronary artery disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina necessitating hospitalization. MACE was analyzed using an ordinal number of metabolic risk factors. Blood pressure of 130/85 mm Hg or treatment with antihypertensive medication, triglyceride concentration of at least 150 mg/dL, HDL cholesterol concentration less than 40 mg/dL for men and 50 mg/dL for women, fasting plasma glucose concentration of at least 100 mg/dL or treatment with glucose-lowering medication, and BMI of at least 30 kg/m2 were all considered metabolic risk factors. The number of metabolic risk factors was used to determine the risk of MACE and the effect of alirocumab. About 3,882 (41%) of the 9,462 patients in the alirocumab group and 3,859 (41%) of the 9462 patients in the placebo group had three or more metabolic risk factors. MACE incidence increased monotonically in the placebo group with each metabolic risk factor, from 7.8% (no risk factors) to 19.6% (5 risk factors; HR 1.18; 95% CI 1.13–1.24 per metabolic risk factor). Alirocumab reduced the relative risk of MACE across categories defined by the number of metabolic risk factors (pinteraction=0.77). Still, the absolute risk reduction (aRR) increased with the number of metabolic risk factors (no risk factors aRR 0.7%, –1.81 to 3.29 vs. 5 risk factors aRR 3.9%, –1.45 to 9.25;pinteraction<0.001). In patients with the recent acute coronary syndrome, the accumulation of metabolic risk variables was linked to an increased risk of MACE. Alirocumab significantly reduced MACE. However, aRR increased as the number of metabolic risk variables increased.