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Comment & Response
May 1, 2019

Interindividual and Intraindividual Responses to PCSK9 Inhibition—Reply

Author Affiliations
  • 1TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
JAMA Cardiol. 2019;4(6):600-601. doi:10.1001/jamacardio.2019.1200

In Reply Thompson raises the possibility of intraindividual variation in the magnitude of low-density lipoprotein cholesterol (LDL-C) reduction with proprotein convertase subtilisin/kexin type 9 inhibitors based on timing of measurement of LDL-C after administration of the drug and cites an intriguing case report with alirocumab with apparent waning of effect from day 1 to day 13.1 Although the focus in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk trial, a global cardiovascular outcomes study involving 27 564 patients, was not serial pharmacodynamic measurements, the LDL-C measurements we presented were to have been obtained at the end of the dosing interval and thus should represent the trough of pharmacodynamic effect.2 Our group and others have reported that the top doses of evolocumab reduce LDL-C levels on average by as much as 85% at the midpoint of the dosing interval and by 60% at the end of dosing interval.3-5

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