Effect of PCSK9 Inhibition With Alirocumab in Patients With Probable Familial Hypercholesterolemia or Type III Hyperlipoproteinemia: Results From the ODYSSEY OUTCOMES Trial

Background In this post hoc analysis of the ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, we evaluated the efficacy of alirocumab in patients with probable heterozygous familial hypercholesterolemia (HeFH) or type III hyperlipoproteinemia (T3HLP). Methods Patients had clinical HeFH if baseline low‐density lipoprotein cholesterol was ≥250 mg/dL and the qualifying acute coronary syndrome event occurred before age 55 (men) or 60 years (women), or if baseline low‐density lipoprotein cholesterol was ≥330 mg/dL. Patients had T3HLP if the ratio, validated using the UK Biobank database, of non–high‐density lipoprotein cholesterol/apolipoprotein B was >2.6. Genetic variation affecting low‐density lipoprotein cholesterol levels (HeFH) and APOE genotypes (T3HLP) was assessed in a pharmacogenomics subgroup. Results In total, 5.8% of patients from ODYSSEY OUTCOMES and 5.9% from the pharmacogenomics subgroup qualified as having clinical HeFH. In the pharmacogenomics subgroup, 295 patients (2.5%) had genetically confirmed HeFH; 45.8% also qualified as having clinical HeFH. Lipid responses and clinical benefits of alirocumab were similar in all patients with or without HeFH. In the ODYSSEY OUTCOMES cohort, 30 of 18 924 patients (0.16%) were identified as having T3HLP. The pharmacogenomics subgroup included 13 of these 30 patients, of whom 7 (53.8%) were APOE2/2 homozygotes. Lipid responses to alirocumab in patients with T3HLP were comparable with those in the general population. In those with genetic dyslipidemia, adverse event incidence was similar to the overall group. Conclusions In ODYSSEY OUTCOMES, individuals with HeFH were common while those with T3HLP were rare. In their lipid responses, carriers of both conditions benefited from alirocumab. Registration URL: https://clinicaltrials.gov ; Unique identifier: NCT01663402.