Highlights
- •The effectiveness of PCSK9 inhibition therapy in a real-world context was -66%.
- •The relative LDL-C change was significantly higher in men (-70%) than women (-59%).
- •The absolute LDL-C change was not significantly different between men and women.
- •In women, older age did not modify PCSK9 inhibitor efficacy for decreasing LDL-C.
- •With high-intensity statin, both sexes reached treatment target with PCSK9 inhibitor.
Abstract
Background
Objectives
Methods
Results
Conclusion
KEYWORDS
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- 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the american college of cardiology/american heart association task force on clinical practice guidelines.Circulation. 2019; 139: e1082-ee143
- Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials.Lancet. 2010; 376: 1670-1681
- Interpretation of the evidence for the efficacy and safety of statin therapy.Lancet. 2016; 388: 2532-2561
- IMPROVE-IT Investigators. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes.N Engl J Med. 2015; 372: 2387-2397
- LDL cholesterol target achievement in heterozygous familial hypercholesterolemia patients according to 2019 ESC/EAS lipid guidelines: Implications for newer lipid-lowering treatments.Int J Cardiol. 2021; 345: 119-124
- Attainment of LDL-Cholesterol Treatment Goals in Patients With Familial Hypercholesterolemia: 5-Year SAFEHEART Registry Follow-Up.J Am Coll Cardiol. 2016; 67: 1278-1285
- Meta-analysis of comparative efficacy of increasing dose of Atorvastatin versus Rosuvastatin versus Simvastatin on lowering levels of atherogenic lipids (from VOYAGER).Am J Cardiol. 2010; 105: 69-76
- FOURIER steering committee and investigators. evolocumab and clinical outcomes in patients with cardiovascular disease.N Engl J Med. 2017; 376: 1713-1722
- ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome.N Engl J Med. 2018; 379: 2097-2107
Center for Drugs Evaluation and Research /FDA. (2015, 30 septembre). https://fda.report/media/97221/Praluent-Statistical-Review-and-Evaluation.pdf. Reference ID: 3827120.
Center for Drugs Evaluation and Research /FDA. (2015, 26 octobre). https://fda.report/media/97009/Staistical-Review-and-Evaluation–Repatha-%28evolocumab%29.pdf. Reference ID: 3838359.
- SAFEHEART investigators. Efficacy of PCSK9 inhibitors in the treatment of heterozygous familial hypercholesterolemia: a clinical practice experience.J Clin Lipidol. 2021; 15: 584-592
- Sex differences in low-density lipoprotein cholesterol reduction with PCSK9 Inhibitors in Real-world patients: the LIPID-REAL registry.J Cardiovasc Pharmacol. 2022; 79: 523-529
- PCSK9 deficiency unmasks a sex- and tissue-specific subcellular distribution of the LDL and VLDL receptors in mice.J Lipid Res. 2015; 56: 2133-2142
- Genetic and metabolic determinants of plasma PCSK9 levels.J Clin Endocrinol Metab. 2009; 94: 2537-2543
- Influence of physiological changes in endogenous estrogen on circulating PCSK9 and LDL cholesterol.J Lipid Res. 2015; 56: 463-469
- The effects of estrogen on serum level and hepatocyte expression of PCSK9.Metabolism. 2015; 64: 554-560
- Relationship between testosterone, estradiol and circulating PCSK9: Cross-sectional and interventional studies in humans.Clin Chim Acta. 2015; 446: 97-104
- Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Genet Med. 2015; 17: 405-424
- Six years' experience with LipidSeq: clinical and research learnings from a hybrid, targeted sequencing panel for dyslipidemias.BMC Med Genomics. 2020; 13: 23
- 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults.Can J Cardiol. 2021; 37: 1129-1150
- 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardio- vascular risk.Eur Heart J. 2020; 41: 111-188
- Unusual responses to PCSK9 inhibitors in a clinical cohort utilizing a structured follow-up protocol.Am J Prev Cardiol. 2020; 1100012
- Lipoprotein (a): impact by ethnicity and environmental and medical conditions.J Lipid Res. 2016; 57: 1111-1125
- Elevated circulating PCSK9 concentrations predict subclinical atherosclerotic changes in low risk obese and non-obese patients.Cardiol Ther. 2017; 6: 281-289
- Lipid lowering therapy and circulating PCSK9 concentration.J Atheroscler Thromb. 2017; 24: 895-907
- Women living with familial hypercholesterolemia: challenges and considerations surrounding their care.Curr Atheroscler Rep. 2020; 22: 60
- Race/ethnic and sex differences in the initiation of non-statin lipid-lowering medication following myocardial infarction.J Clin Lipidol. 2021; 15: 665-673
- Proprotein convertase subtilisin/kexin type 9 inhibitor utilization and low-density lipoprotein-cholesterol control in familial hypercholesterolemia.J Clin Lipidol. 2021; 15: 339-346
Article info
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Author contributions: Conceptualization: S.B. (lead), S.F. (supporting); Supervision: S.B. (lead), M.P. (supporting); Data collection: N. S-P. (lead), S.F. (lead) and M.P. (supporting); Data curation: M.P.; Formal analysis: M.P.; Project administration: M.P.; Analysis and interpretation of data: All authors; Writing - Original Draft: M.P.; Writing - Review & Editing: All authors; Final approval of the version to be published: All authors; Agreement to act as guarantor of the work: All authors; Dr. Bernard had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis
Conflict of interest: A.B. received research grants from Akcea, Amgen, Astra Zeneca, Fondation Leducq, Fondation Yvan Morin, Merck Frosst and Sanofi. He has participated in clinical research protocols from Acasti Pharma Inc., Akcea, Amgen, Astra Zeneca, Ionis Pharmaceuticals, Inc., The Medicines Company, Merck Frosst, Novartis, Pfizer, Regeneron Pharmaceuticals Inc. and Sanofi. He has served on advisory boards and received honoraria for symposia from Akcea, Amgen and Sanofi. S.B. received research grants from Akcea, Fondation Leducq and Fondation Yvan Morin. She has participated in clinical research protocols from Akcea, Amgen, Ionis Pharmaceuticals, Inc., The Medicines Company, Novartis, Pfizer and Sanofi. She has served on advisory boards for Akcea, Amgen, HLS Therapeutics, Novartis, Novo Nordisk and Sanofi, and received honoraria for symposia from Akcea, Amgen, Novo Nordisk and Sanofi. N.S-P. participated in advisory boards for Akcea in 2018 and received honoraria. M.P. and S.F. have nothing to declare.
Funding sources: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.