The Effect of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition on Sterol Absorption Markers in a Cohort of Real-World Patients

Abstract

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is expressed in multiple tissues, including the small intestine. The effect of PCSK9 inhibition on cholesterol absorption is not known. Objectives: Measure serum cholesterol absorption markers before and after initiation of PCSK9 inhibitors. Methods: Single-center retrospective cohort of patients administered evolocumab and alirocumab between July 2015 and January 2017. Paired t tests were used to compare mean serum cholesterol marker concentrations, and ratios to total cholesterol, before and after PCSK9 inhibitor initiation. Analyses were repeated for those taking and not taking statins and taking or not taking ezetimibe at both initiation and follow-up, for each PCSK9 inhibitor, and based on follow-up time (<60, 60-120, and >120 days). Results: There were 62 possible participants, 34 were excluded for lack of data or unknown PCSK9 inhibitor initiation date. Average follow-up was 92.5 days. Mean campesterol (before 3.14 μg/mL, 95% CI: 2.79-4.38 μg/mL; after 2.09 μg/mL, 95% CI: 1.87-2.31 μg/mL; P < .0001), sitosterol (before 2.46 μg/mL, 95% CI: 2.23-2.70 μg/mL; after 1.62 μg/mL, 95% CI: 1.48-1.75 μg/mL; P < .0001), and cholestanol (before 3.25 μg/mL, 95% CI: 3.04-3.47 μg/mL; after 2.08 μg/mL, 95% CI: 1.96-2.21 μg/mL; P < .0001) all significantly decreased at follow-up. There was no significant change in absorption marker to total cholesterol ratios. Findings were not influenced by statin or ezetimibe use or nonuse, which PCSK9 inhibitor was prescribed, or time to follow-up. Conclusion: Proprotein convertase subtilisin/kexin type 9 inhibition was associated with decreased cholesterol absorption markers.