evolocumab (Repatha)
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Indications
- coronary artery disease
- lowers risk major adverse cardiovascular events (RR=0.47)
- lowers risk of cardiovascular events & cardiovascular mortality in statin-treated patients with cardiovascular disease & LDL cholesterol > 70 mg/dL[7]
- no difference in all cause mortality[7]
- mixed hyperlipidemia[3]
- familial hypercholesterolemia (FDA approved Aug 2015)[4]
- FDA-approved (Dec 2017) for prevention of heart attacks, strokes, & coronary revascularizations in patients with established cardiovascular disease[10]
* ezetimibe 1st line added to high-potency statin[13]
Dosage
Adverse effects
- addition of evolocumab to statin therapy does not adversely affect cognitive function within 2 years with LDL cholesterol as low as 30 mg/dL[8][11]
- does not worsen diabetes or increase risk of developing diabetes within 2 years[9]
- increased risk of cardiac death[12]
- drug adverse effects of anti-hyperlipidemic agents
- drug adverse effects of PCSK9 inhibitor(s)
- drug adverse effects of pharmaceutical monoclonal antibodies
Mechanism of action
- PCSK9 inhibitor
- human monoclonal IgG2 antibody directed against PCSK9
- lowers LDL cholesterol in patients receiving statin therapy 36 mg/dL vs 93 mg/dL[6]
- induces coronary atheroma regression in 2/3 of patients[6]
Notes
More general terms
References
- ↑ Sabatine MS et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 2015 Mar 15 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25773607 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1500858
- ↑ 2.0 2.1 Husten L, Di Francesco S Success of Two New Cholesterol Drugs May Come Down to Convenience, Dosing, and Cost. Physician's First Watch, May 27, 2015 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
- ↑ 3.0 3.1 Rosenson R Jacobson T, Preiss D, et al. Efficacy and safety of the PCSK9 inhibitor evolocumab in patients with mixed hyperlipidemia. International Symposium on Atherosclerosis 2015; May 26, 2015; Amsterdam, the Netherlands. Abstract 0252 http://www.eventure-online.com/eventure/publicAbstractView.do?id=259016&congressId=8753
- ↑ 4.0 4.1 Young K, Saitz R FDA Advisers Recommend First-in-Class Cholesterol-Lowering Meds Physician's First Watch, June 11, 2015 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
Briefing Information for the June 10, 2015 Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/ucm450071.htm
O'Riordan M FDA Green-lights Evolocumab (Repatha) for LDL-Cholesterol Lowering. Medscape Oncology. August 27, 2015 http://www.medscape.com/viewarticle/850043
FDA News Release. August 27, 2015 FDA approves Repatha to treat certain patients with high cholesterol. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm460082.htm - ↑ Prescriber's Letter 22(8): 2015 PCSK9 Inhibitors for High Cholesterol Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=310813&pb=PRL http://www.prescribersletter.com (subscription needed)
- ↑ 6.0 6.1 6.2 Nicholls SJ, Puri R, Anderson T et al Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial. JAMA. Published online Nov 15, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27846344 <Internet> http://jamanetwork.com/journals/jama/fullarticle/2584184
- ↑ 7.0 7.1 7.2 Sabatine MS, Giugliano RP, Keech AC et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017 Mar 17; PMID: https://www.ncbi.nlm.nih.gov/pubmed/28304224
- ↑ 8.0 8.1 Giugliano RP, Mach F, Zavitz K et al Cognitive Function in a Randomized Trial of Evolocumab. N Engl J Med 2017; 377:633-643. August 17, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28813214 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1701131
- ↑ 9.0 9.1 Busko M Evolocumab Doesn't Worsen Glycemia or Up Diabetes Risk: FOURIER Medscape - Sep 19, 2017. http://www.medscape.com/viewarticle/885882
- ↑ 10.0 10.1 Lou N. Repatha Wins FDA Approval for Stand-Alone CVD Prevention - Will more patients now gain access to PCSK9 inhibitors? MedPage Today, Dec 01, 2017 https://www.medpagetoday.com/cardiology/prevention/69627
Brooks M FDA Approves Evolocumab (Repatha) to Prevent CV Events. Medscape - Dec 01, 2017. https://www.medscape.com/viewarticle/889513 - ↑ 11.0 11.1 Gencer B et al. Cognition after lowering LDL-cholesterol with evolocumab. J Am Coll Cardiol 2020 May 12; 75:2283. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32381158 https://www.sciencedirect.com/science/article/abs/pii/S0735109720346544
Robinson JG. Low LDL-C levels: Likely no short-term cognitive harm. J Am Coll Cardiol 2020 May 12; 75:2294 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32381159 https://www.sciencedirect.com/science/article/abs/pii/S073510972034657X - ↑ 12.0 12.1 Erviti J, Wright J, Bassett K et al Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: a reanalysis based on regulatory data. BMJ Open. 2022. 12(12) PMID: https://www.ncbi.nlm.nih.gov/pubmed/36585131 PMCID: PMC9809302 Free PMC article https://bmjopen.bmj.com/content/12/12/e060172
- ↑ 13.0 13.1 Aguilar-Salinas CA, Gomez-Diaz RA, Corral P. New therapies for primary hyperlipidemia. J Clin Endocrinol Metab. 2022;107:1216-1224. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34888679