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

Abstract

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 < 0.001, n = 19). P-selectin and vascular endothelial growth factors remained unchanged. Flow-dependent dilatation of the brachial artery (+41%, 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.

Non-Lipid Effects of PCSK9 Monoclonal Antibodies on Vessel Wall

“…The decrease of Lp(a) in their study was 7%, which is statistically important (p = 0.002), but not predictive for FMD improvement. On the other hand, treatment with alirocumab for 10 weeks in the ALIROCKS trial showed a nominal amelioration (+41%), but no significant change of flow-dependent dilatation of the brachial artery [47]. The sample size and duration of treatment with PCSK9 inhibitors were similar among the mentioned studies.…”

Effects of PCSK9 on thrombosis and haemostasis in a variety of metabolic states: Lipids and beyond (Review)

“…Inflammation induced by endothelial dysfunction abnormally induces platelet attachment to endothelial cells in the arterial walls ( 100 ), increasing the cardiovascular risk. Even with short-term treatment, the PCSK9 inhibitors, evolocumab and alirocumab, have been found to improve endothelial function ( 101 , 102 ). Damage to the vascular wall by PCSK9 can occur via a variety of mechanisms.…”

The Anti-Thrombotic Effects of PCSK9 Inhibitors

“…The result was that vascular endothelial growth factors and P-selectin did not alter. Although flow-dependent dilatation was somewhat improved, there were no discernible long-term benefits of PCSK9 inhibitor therapy on vascular function [ 68 ]. A specific analysis of the ODYSSEY Outcomes trial ( n = 18,924 patients with acute coronary syndromes) showed a reduction in major advanced cardiovascular events (MACE).…”