Advances in dyslipidemia management for prevention of atherosclerosis: PCSK9 monoclonal antibody therapy and beyond

Cardiovascular Diagnosis and Therapy
Nathan D WongRobert S Greenfield

Abstract

In 2003, select families with familial hypercholesterolemia were first identified to have gain-of-function mutations for proprotein convertase subtilisin kexin type 9 (PCSK9) followed, in 2006, by the identification of those with lifelong low levels of LDL-C and lowered atherosclerotic cardiovascular disease (ASCVD) risk who had loss-of-function PCSK9 mutations. These discoveries led to the rapid development of PSCK9-targeted monoclonal antibody (PCSK9 mAb) therapies and, in 2015, 2 'fully-humanized' PCSK9 mAbs (alirocumab and evolocumab) were marketed in the United States, Europe, and other countries. In a wide range of high risk patients, with and without ASCVD, these PCSK9 mAbs, as once or twice monthly subcutaneous injections, potently reduce LDL-C 50-65% beyond levels achieved by maximally tolerated statin therapy; approximately one-third of patients achieve LDL-C levels <25 mg/dL. In the US, PCSK9 mAb therapy has current limited indications for persons with ASCVD or familial hypercholesterolemia requiring additional LDL-C reduction beyond maximally tolerated statin therapy. The first of the ASCVD outcomes-driven trials, the FOURIER trial has very recently shown in over 27,000 subjects randomized to evolocumab or placebo o...Continue Reading

Citations

Jan 25, 2018·Pharmacy : Journal of Pharmacy, Education and Practice·Donatella ZoddaSilvia Schifilliti
Oct 11, 2019·BioFactors·Eskandar TaghizadehAlireza Pasdar
Mar 22, 2019·Frontiers in Cardiovascular Medicine·Nathan D Wong, Michael D Shapiro
Dec 13, 2017·Frontiers in Genetics·Parisa NaeliSeyed J Mowla
May 23, 2019·Current Cardiology Reviews·Romeo-Gabriel Mihăilă
Nov 2, 2019·Clinics in Laboratory Medicine·Hugues Allard-Chamard
Jul 3, 2021·Medical Sciences : Open Access Journal·Sanjay KalraPawan Rawal

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