Effects of Alirocumab on Triglyceride Metabolism: A Fat-Tolerance Test and Nuclear Magnetic Resonance Spectroscopy Study
Thomas Metzner,
Deborah R. Leitner,
Karin Mellitzer,
Andrea Beck,
Harald Sourij,
Tatjana Stojakovic,
Gernot Reishofer,
Winfried März,
Ulf Landmesser,
Hubert Scharnagl,
Hermann Toplak,
Günther Silbernagel
Affiliations
Thomas Metzner
Department of Internal Medicine, Division of Angiology, Medical University of Graz, 8036 Graz, Austria
Deborah R. Leitner
Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, 8036 Graz, Austria
Karin Mellitzer
Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, 8036 Graz, Austria
Andrea Beck
Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, 8036 Graz, Austria
Harald Sourij
Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, 8036 Graz, Austria
Tatjana Stojakovic
Clinical Institute of Medical and Chemical Laboratory Diagnostics, University Hospital Graz, 8036 Graz, Austria
Gernot Reishofer
Department of Radiology, Clinical Division of Neuroradiology, Vascular and Interventional Radiology, Medical University of Graz, 8036 Graz, Austria
Winfried März
Department of Internal Medicine 5 (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Mannheim Medical Faculty, University of Heidelberg, 68167 Mannheim, Germany
Ulf Landmesser
German Center for Cardiovascular Research (DZHK)-Partner Site Berlin, Department of Cardiology, Berlin Institute of Health, Charité University Medicine Berlin, 12200 Berlin, Germany
Hubert Scharnagl
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8036 Graz, Austria
Hermann Toplak
Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, 8036 Graz, Austria
Günther Silbernagel
Department of Internal Medicine, Division of Angiology, Medical University of Graz, 8036 Graz, Austria
Background: PCSK9 antibodies strongly reduce LDL cholesterol. The effects of PCSK9 antibodies on triglyceride metabolism are less pronounced. The present study aimed to investigate in detail the effects of alirocumab on triglycerides, triglyceride-rich lipoproteins, and lipase regulators. Methods: A total of 24 patients with an indication for treatment with PCSK9 antibodies were recruited. There were two visits at the study site: the first before initiation of treatment with alirocumab and the second after 10 weeks of treatment. Fat-tolerance tests, nuclear magnetic resonance spectroscopy, and enzyme-linked immunosorbent assays were performed to analyze lipid metabolism. Results: A total of 21 participants underwent the first and second investigation. Among these, two participants only received alirocumab twice and 19 patients completed the trial per protocol. All of them had atherosclerotic vascular disease. There was no significant effect of alirocumab treatment on fasting triglycerides, post-prandial triglycerides, or lipoprotein-lipase regulating proteins. Total, large, and small LDL particle concentrations decreased, while the HDL particle concentration increased (all p p < 0.001). Whereas PCSK9 increased more than three-fold in all 19 compliant patients, it remained unchanged in those two patients with two injections only. Conclusion: Significant effects of alirocumab on triglyceride metabolism were not detectable in the ALIROCKS trial. The total circulating PCSK9 concentration might be a useful biomarker to differentiate non-adherence from non-response to PCSK9 antibodies.
