Author(s)
Joshua O. Holmes, PharmD, MS
Amanda Scharlet, PharmD, BCACP

Reviewed By
Dawn C. Fuke, PharmD, BCPS
Evan M. Sisson, PharmD, MSHA, BCACP, CDCES

Citation
Ray KK, Phil M, Wright RS et al. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol. N Engl J Med. 2020;382:1507-1519

The Problem

While significant medical advancements have led to a decline in mortality from cardiovascular disease, it remains the leading cause of death in the United States.1 Lipid management continues to be an essential component in prevention and treatment of atherosclerotic cardiovascular disease (ASCVD), but for the past decade, clinical practice guidelines have gone back and forth about optimal treatment goals. One thing guidelines do agree on is that statins are preferred initial therapy. However, there has been a shift in recommendations about optimal add-on therapies.2-4

What’s Known

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  1. Table 5. Age-adjusted death rates for selected causes of death, by sex, race, and Hispanic origin: United States, selected years 1950-2017 [Internet].  Atlanta (GA): Centers for Disease Control and Prevention; 2018 [cited 2020 June 12]. Available from:  https://www.cdc.gov/nchs/data/hus/2018/005.pdf
  2. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III) JAMA. 2001;285:2486–97.
  3. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2889-934.
  4. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. Circulation. 2019;139:e1082–e1143.
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  6. Hess CN, Wang CCL, Hiatt WR.  PCSK9 inhibitors: mechanisms of action, metabolic effects, and clinical outcomes. Annu Rev Med. 2018;68:133-45.
  7. Sabatine MS, Guigliano RP, Keech AC et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713-22.
  8. Robinson JG, Farnier M, Kremph M et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1489-99.
  9. Ridker PM, Revkin J, Amarenco P, et al. Cardiovascular efficacy and safety of bococizumab in high-risk patients. N Engl J Med. 2017;376:1527-39
  10. Ray KK, Phil M, Wright RS et al.  Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol.  N Engl J Med. 2020:1-12.
  11. Ray KK, Landmesser U, Leiter LA, et al. Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol. N Engl J Med. 2017;376:1430-1440.
  12. Kannel WB, Neaton JD, Wentworth D, et al. Overall and coronary heart disease mortality rates in relation to major risk factors in 325,348 men screened for the MRFIT. Multiple Risk Factor Intervention Trial. Am Heart J. 1986;112:825-36.
  13. University of Oxford. A randomized trial assessing the effects of inclisiran on clinical outcomes among people with cardiovascular disease (ORION-4). Available from: https://www.clinicaltrials.gov/ct2/show/NCT03705234?term=inclisiran&draw=2&rank=8. Identifier: NCT03705234. Accessed April 30, 2020.