| Title: | Effect of PCSK9 Inhibition With Alirocumab in Patients With Probable Familial Hypercholesterolemia or Type III Hyperlipoproteinemia: Results From the ODYSSEY OUTCOMES Trial |
| Journal: | Journal of the American Heart Association |
| Published: | 22 Aug 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40847481/ |
| DOI: | https://doi.org/10.1161/jaha.124.041190 |
| URL: | https://www.ahajournals.org/doi/pdf/10.1161/JAHA.124.041190 |
Publication 19698
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
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).</p>
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.</p>
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.</p>
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.</p>
REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT01663402.</p>
18 Keywords
- Acute Coronary Syndrome
- Aged
- Antibodies, Monoclonal, Humanized
- Anticholesteremic Agents
- Apolipoproteins E
- Biomarkers
- Cholesterol, LDL
- Female
- Heterozygote
- Humans
- Hyperlipoproteinemia Type II
- Hyperlipoproteinemia Type III
- Male
- Middle Aged
- PCSK9 Inhibitors
- Proprotein Convertase 9
- Serine Proteinase Inhibitors
- Treatment Outcome
15 Authors
- Gregory P. Geba
- Kusha A. Mohammadi
- Amy Damask
- Charles Paulding
- Luca A. Lotta
- George Hindy
- Robert Pordy
- Garen Manvelian
- Michael D. Shapiro
- Vera A. Bittner
- Deepak L. Bhatt
- Michael Szarek
- Gregory G. Schwartz
- Ph. Gabriel Steg
- Sergio Fazio
Enabling scientific discoveries that improve human health