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evolocumab (Repatha)

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: - 140 mg SQ biweekly or 420 mg SQ monthly 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] 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: - established differences in health outcomes relative to statins alone [2]

Interactions

drug adverse effects of anti-hyperlipidemic agents

General

PCSK9 inhibitor (ALN-PCS) pharmaceutical monoclonal antibody

References

  1. Sabatine MS et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 2015 Mar 15 PMID: 25773607 http://www.nejm.org/doi/full/10.1056/NEJMoa1500858
  2. 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. 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. 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
  5. Prescriber's Letter 22(8): 2015 PCSK9 Inhibitors for High Cholesterol Detail-Document#: 310813 http://www.prescribersletter.com (subscription needed)
  6. 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 PMID: 27846344 http://jamanetwork.com/journals/jama/fullarticle/2584184
  7. 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: 28304224
  8. 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 PMID: 28813214 http://www.nejm.org/doi/full/10.1056/NEJMoa1701131
  9. Busko M Evolocumab Doesn't Worsen Glycemia or Up Diabetes Risk: FOURIER Medscape - Sep 19, 2017. http://www.medscape.com/viewarticle/885882
  10. 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. Gencer B et al. Cognition after lowering LDL-cholesterol with evolocumab. J Am Coll Cardiol 2020 May 12; 75:2283. PMID: 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: 32381159 https://www.sciencedirect.com/science/article/abs/pii/S073510972034657X
  12. 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: 36585131 PMCID: PMC9809302 Free PMC article https://bmjopen.bmj.com/content/12/12/e060172
  13. Aguilar-Salinas CA, Gomez-Diaz RA, Corral P. New therapies for primary hyperlipidemia. J Clin Endocrinol Metab. 2022;107:1216-1224. PMID: 34888679