Short-Term Treatment with Alirocumab, Flow-Dependent Dilatation of the Brachial Artery and Use of Magnetic Resonance Diffusion Tensor Imaging to Evaluate Vascular Structure: An Exploratory Pilot Study
Thomas Metzner,
Deborah R. Leitner,
Gudrun Dimsity,
Felix Gunzer,
Peter Opriessnig,
Karin Mellitzer,
Andrea Beck,
Harald Sourij,
Tatjana Stojakovic,
Hannes Deutschmann,
Winfried März,
Ulf Landmesser,
Marianne Brodmann,
Gernot Reishofer,
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
Gudrun Dimsity
Department of Internal Medicine, Division of Angiology, Medical University of Graz, 8036 Graz, Austria
Felix Gunzer
Department of Radiology, Clinical Division of Neuroradiology, Vascular and Interventional Radiology, Medical University of Graz, 8036 Graz, Austria
Peter Opriessnig
Department of Radiology, Clinical Division of Neuroradiology, Vascular and Interventional Radiology, 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
Hannes Deutschmann
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
Marianne Brodmann
Department of Internal Medicine, Division of Angiology, Medical University of Graz, 8036 Graz, Austria
Gernot Reishofer
Department of Radiology, Clinical Division of Neuroradiology, Vascular and Interventional Radiology, Medical University of Graz, 8036 Graz, Austria
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: Short-term effects of alirocumab on vascular function have hardly been investigated. Moreover, there is a scarce of reliable non-invasive methods to evaluate atherosclerotic changes of the vasculature. The ALIROCKS trial was performed to address these issues using standard ultrasound-based procedures and a completely novel magnetic resonance-based imaging technique. Methods: A total of 24 patients with an indication for treatment with PCSK9 antibodies were recruited. There were 2 visits to the study site, the first before initiation of treatment with alirocumab and the second after 10 weeks of treatment. The key outcome measures included the change of carotid vessel wall fractional anisotropy, a novel magnetic resonance-based measure of vascular integrity, and the changes of carotid intima-media thickness and flow-dependent dilatation of the brachial artery measured with ultrasound. Results: A total of 19 patients completed the trial, 2 patients stopped treatment, 3 patients did not undergo the second visit due to the COVID pandemic. All of them had atherosclerotic vascular disease. Their mean (standard deviation) LDL-cholesterol concentration was 154 (85) mg/dL at baseline and was reduced by 76 (44) mg/dL in response to alirocumab treatment (p p = 0.241, n = 18), carotid intima-media thickness (p = 0.914, n = 18), and fractional anisotropy of the carotid artery (p = 0.358, n = 13) also did not significantly change. Conclusion: Despite a nominal amelioration for flow-dependent dilatation, significant effects of short-term treatment with alirocumab on vascular function were not detectable. More work would be needed to evaluate, whether fractional anisotropy may be useful in clinical atherosclerosis research.
