Nicholls Stephen J, Nissen Steven E, Prati Francesco, Windecker Stephan, Kataoka Yu, Puri Rishi, Hucko Thomas, Kassahun Helina, Liao Jason, Somaratne Ransi, Butters Julie, Di Giovanni Giuseppe, Jones Stephen, Psaltis Peter J
Monash Cardiovascular Research Centre, Clayton, Australia.
Cardiovasc Diagn Ther. 2021 Feb;11(1):120-129. doi: 10.21037/cdt-20-684.
Technological advances in arterial wall imaging permit the opportunity to visualize coronary atherosclerotic plaque with sufficient resolution to characterize both its burden and compositional phenotype. These modalities have been used extensively in clinical trials to evaluate the impact of lipid lowering therapies on serial changes in disease burden. While the findings have unequivocally established that these interventions have the capacity to either slow disease progression or promote plaque regression, depending on the degree of lipid lowering achieved, their impact on plaque phenotype is less certain. More recently optical coherence tomography (OCT) has been employed with a number of studies demonstrating favorable effects on both fibrous cap thickness (FCT) and the size of lipid pools within plaque in response to statin treatment.
The phase 3, multi-center, double-blind HUYGENS study will assess the impact of incremental lipid lowering with the proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor, evolocumab, on plaque features using serial OCT imaging, in statin-treated patients following an acute coronary syndrome (ACS). Subjects with non-ST-elevation ACS (n=150) will be randomized 1:1 into two groups to receive monthly injections of evolocumab 420 mg or placebo.
The primary endpoint is the effect of evolocumab on coronary atherosclerotic plaques will be assessed by OCT at baseline and at week 50.
The HUYGENS study will determine whether intensified lipid lowering therapy with evolocumab in addition to maximally tolerated statin therapy will have incremental benefits on high-risk features of coronary artery plaques.
This study was registered on Clinicaltrials.gov (NCT03570697).
动脉壁成像技术的进步使得有机会以足够的分辨率可视化冠状动脉粥样硬化斑块，从而对其负荷和成分表型进行表征。这些方法已在临床试验中广泛用于评估降脂治疗对疾病负荷系列变化的影响。虽然研究结果明确表明，这些干预措施有能力减缓疾病进展或促进斑块消退，这取决于实现的降脂程度，但其对斑块表型的影响尚不确定。最近，光学相干断层扫描（OCT）已被用于多项研究，这些研究表明，他汀类药物治疗可对斑块内的纤维帽厚度（FCT）和脂质池大小产生有利影响。
3期多中心双盲HUYGENS研究将评估在急性冠状动脉综合征（ACS）后接受他汀类药物治疗的患者中，使用连续OCT成像，前蛋白转化酶枯草溶菌素9型（PCSK9）抑制剂依洛尤单抗逐步降脂对斑块特征的影响。非ST段抬高型ACS患者（n = 150）将按1:1随机分为两组，分别接受每月一次420 mg依洛尤单抗或安慰剂注射。
主要终点是在基线和第50周时通过OCT评估依洛尤单抗对冠状动脉粥样硬化斑块的影响。
HUYGENS研究将确定，在最大耐受他汀类药物治疗的基础上，加用依洛尤单抗强化降脂治疗是否会对冠状动脉斑块的高危特征产生额外益处。
本研究已在Clinicaltrials.gov上注册（NCT03570697）。
