Efficacy of alirocumab for reducing plaque vulnerability: Study protocol for ALTAIR, a randomized controlled trial in Japanese patients with coronary artery disease receiving rosuvastatin

Abstract

Background: Although a recent clinical trial demonstrated that alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, significantly reduces the incidence of acute coronary events, the impact of alirocumab on plaque stabilization remains uncertain. The Efficacy of ALirocumab for Thin-cap fibroatheroma in patients with coronary Artery disease estImated by optical coherence tomogRaphy (ALTAIR) study will investigate the effect of alirocumab on thin-cap fibroatheroma (TCFA) in Japanese patients who underwent recent percutaneous coronary intervention (PCI). Methods and design: ALTAIR is a phase IV, open-label, randomized, parallel-group, single-center study involving blinded optical coherence tomography (OCT) image analysis in Japanese adults hospitalized for PCI and having suboptimal control of low-density lipoprotein cholesterol (LDL-C) levels (>70 mg/dL) despite statin therapy. Patients will be randomized (1:1) to the alirocumab arm (alirocumab 75 mg every 2 weeks added to rosuvastatin 10 mg/day) or the standard-of-care arm (rosuvastatin 10 mg/day, with initiation and/or dose adjustment of non-statin lipid-lowering to achieve an LDL-C target of <70 mg/dL). OCT imaging will be conducted at baseline and at week 36 (post-treatment). The primary objective is to compare the alirocumab and standard-of-care arms regarding the change in TCFA fibrous-cap thickness after 9 months of treatment. Conclusion:The outcomes of ALTAIR (ClinicalTrials.gov identifier: NCT03552432) will provide insights into the effect of alirocumab on plaque vulnerability following PCI in patients with suboptimal LDL-C control despite stable statin therapy.

Effect of alirocumab on coronary plaque in patients with coronary artery disease assessed by optical coherence tomography

“…Furthermore, it is well acknowledged that OCT-defined thin-cap fibroatheroma is correlated with vulnerable plaque characters identified by other imaging techniques [ 35 ], all of which have a strong link to future adverse clinical events [ 23 , 36 ]. Therefore, to date, the increase in fibrous cap thickness has been considered a representation of coronary plaque stabilization [ 37 – 40 ].…”

Impact of PCSK9 Inhibition on Proinflammatory Cytokines and Matrix Metalloproteinases Release in Patients with Mixed Hyperlipidemia and Vulnerable Atherosclerotic Plaque

“…Furthermore, plasma-stabilizing factors for atherosclerotic plaque were identified in one of Otake H.’s investigations, which included patients treated with alirocumab. The authors, however, do not discuss the impact of alirocumab on these parameters in this investigation, instead focusing on the favorable effect of this medication on plaque vulnerability as measured by optical coherence tomography [ 52 ].…”

Impact of Alirocumab on Release Markers of Atherosclerotic Plaque Vulnerability in Patients with Mixed Hyperlipidemia and Vulnerable Atherosclerotic Plaque

“…Moreover, in one of the studies conducted by Otake H., which included patients treated with alirocumab, plasma stabilization factors for atherosclerotic plaque were determined. However, the authors do not describe in this study the influence of alirocumab on these factors, but only describe the positive effect of this therapy on the plaque vulnerability assessed by optical coherence tomography (OCT) [ 51 ].…”