Response by Watts et al to Letter Regarding Article, “Factorial Effects of Evolocumab and Atorvastatin on Lipoprotein Metabolism”
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The FLOREY trial (Effects on Lipoprotein Metabolism From PCSK9 Inhibition Utilizing a Monoclonal Antibody) uniquely demonstrated that evolocumab increases catabolism and lowers production of low-density lipoprotein (LDL) particles.1 The evolocumab dose was chosen to elucidate how maximal inhibition of proprotein convertase subtilisin/kexin type 9 regulates lipoprotein metabolism. Given the comparable ranges of plasma LDL-cholesterol,1,2 it is likely that a similar mode of action of evolocumab applies to changes in atherogenic lipoproteins in the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). Another investigation with a lower dose of alirocumab suggested a similar mechanism in a smaller number of subjects of mixed sex and race.3 Given the primacy of the LDL receptor pathway in controlling …