Author + information
Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of low-density lipoprotein (LDL) receptors, inhibition of which leads to reduced serum LDL. PCSK9 is also present in the small intestine lining where its effect is not well understood, but is thought to increase intestinal triglyceride-rich apoB lipoprotein production, postprandial triglycerides, and chylomicrons, and decrease intestinal cholesterol excretion. As the effect of PCSK9 inhibition on sterol absorption has yet to be reported, we sought to investigate if PCSK9 inhibition in humans alters intestinal sterol absorption markers.
Methods: This was a retrospective cohort study of patients administered evolocumab [Repatha®] or alirocumab [Praluent®] between July 2015 and June 2016. Patients were excluded if they did not have sterol marker data (campesterol, sitosterol, and cholestanol) both prior to and following PCSK9 inhibitor initiation. When results fell below the detection limit, values were estimated as equivalent to the lower limit as to not bias results away from the null. Paired t-tests were used to compare mean serum sterol marker concentrations before and after PCSK9 inhibitor initiation. Analyses were repeated for those taking and not taking statins at both initiation and follow up and for each individual PCSK9 inhibitor.
Results: There were 43 possible subjects, 16 met inclusion criteria. Nine were prescribed evolocumab; 7 were prescribed alirocumab. Average follow up was 64 days. Mean campesterol (before 3.31 μg/mL (95% confidence interval (CI) 2.86 – 3.95 μg/mL), after 2.16 μg/mL, (95% CI 1.88 – 2.61 μg/mL), p = 0.001), sitosterol (before 2.45 μg/mL (95% CI 2.21 – 3.84 μg/mL), after 1.59 μg/mL (95% CI 1.44 – 1.83 μg/mL), p < 0.0001), and cholestanol (before 3.56 μg/mL (95% CI 3.27 – 3.85 μg/mL), after 2.31 μg/mL (95% CI 2.12 – 2.49 μg/mL), p <0.00001) all significantly decreased at follow up. Whether a patient was or was not on a statin over the study period or selection of PCSK9 inhibitor did not significantly influence these findings.
Conclusions: PSCK9 inhibition with evolocumab or alirocumab was associated with decreased sterol absorption markers, regardless of statin use.
Poster Hall, Hall C
Friday, March 17, 2017, 10:00 a.m.-10:45 a.m.
Session Title: Advances in Cholesterol Measurement and Management
Abstract Category: 32. Prevention: Clinical
Presentation Number: 1106-062
- 2017 American College of Cardiology Foundation