Mensink Frans B, Los Jonathan, Oemrawsingh Rohit M, von Birgelen Clemens, Ijsselmuiden Alexander, Meuwissen Martijn, Cheng Jin M, van Wijk Diederik F, Smits Pieter C, Paradies Valeria, van der Heijden Dirk J, Rai Himanshu, Ten Cate Tim Jf, Camaro Cyril, Damman Peter, van Nunen Lokien X, Dimitriu-Leen Aukelien C, van Wely Marleen H, Cetinyurek-Yavuz Aysun, Byrne Robert A, van Royen Niels, van Geuns Robert-Jan M
Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Cardiology, Albert Schweitzer Ziekenhuis, Dordrecht, the Netherlands.
Heliyon. 2024 Sep 18;10(19):e38077. doi: 10.1016/j.heliyon.2024.e38077. eCollection 2024 Oct 15.
Non-culprit coronary artery lesions are commonly present in patients presenting with an acute coronary syndrome (ACS). Additional stenting of non-culprit lesions in addition to the culprit lesion intends to prevent secondary events caused by these lesions. At the same time, multiple trials have demonstrated the potential of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in reducing plaque size and changing plaque composition of non-culprit lesions. Whether intensive low-density lipoprotein cholesterol (LDL-C) reduction with PCSK9 inhibitor evolocumab improves non-culprit vessel hemodynamics, reduces the risk of plaque rupture of important non-culprit lesions, and might obviate the need for additional stenting has not been investigated. The "Functional Improvement of non-infarcT related coronary artery stenosis by Extensive LDL-C Reduction with a PCSK9 Antibody" (FITTER) trial is a multi-center, randomized, double-blind, placebo-controlled clinical trial for patients presenting with ACS and multivessel disease (MVD). After treatment of the culprit lesion, fractional flow reserve (FFR) is performed in non-culprit vessels amenable for percutaneous coronary intervention (PCI). Coronary intervention in patients with hemodynamically important non-critical lesions (FFR: 0.67-0.85) is staged after baseline imaging using near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS). Eligible patients are randomized and treated for 12 weeks with either evolocumab or placebo, in addition to high-intensity statin therapy. Follow-up angiography with repeat FFR and IVUS-NIRS is scheduled at 12 weeks. Staged PCI is performed at the operator's discretion.The FITTER trial is the first study to evaluate the effect of maximal LDL-C reduction by the PCSK9 inhibitor evolocumab on invasively measured FFR, plaque size, and plaque composition in hemodynamically important non-culprit lesions, during a treatment period of just 12 weeks after an ACS. Currently, all patients have been included (August 2023) and data analysis is ongoing.
clinicaltrials.gov NCT04141579.
非罪犯冠状动脉病变常见于急性冠状动脉综合征（ACS）患者。除罪犯病变外，对非罪犯病变进行额外支架置入旨在预防这些病变引起的继发事件。同时，多项试验已证明前蛋白转化酶枯草溶菌素/ kexin 9型（PCSK9）抑制剂在减小非罪犯病变的斑块大小和改变斑块成分方面的潜力。使用PCSK9抑制剂依洛尤单抗进行强化低密度脂蛋白胆固醇（LDL-C）降低是否能改善非罪犯血管的血流动力学、降低重要非罪犯病变的斑块破裂风险以及是否可能无需额外支架置入尚未得到研究。“通过PCSK9抗体广泛降低LDL-C改善非梗死相关冠状动脉狭窄的功能”（FITTER）试验是一项针对患有ACS和多支血管病变（MVD）患者的多中心、随机、双盲、安慰剂对照临床试验。在处理罪犯病变后，对适合经皮冠状动脉介入治疗（PCI）的非罪犯血管进行血流储备分数（FFR）测量。使用近红外光谱（NIRS）和血管内超声（IVUS）在基线成像后对血流动力学重要的非临界病变（FFR：0.67 - 0.85）患者进行分期冠状动脉介入治疗。符合条件的患者除接受高强度他汀类药物治疗外，随机接受依洛尤单抗或安慰剂治疗12周。计划在12周时进行随访血管造影并重复FFR和IVUS - NIRS检查。分期PCI由术者自行决定。FITTER试验是第一项评估PCSK9抑制剂依洛尤单抗在ACS后仅12周的治疗期内对血流动力学重要的非罪犯病变进行侵入性测量的FFR、斑块大小和斑块成分的最大LDL-C降低效果的研究。目前，所有患者均已纳入（2023年8月），数据分析正在进行中。
clinicaltrials.gov NCT04141579
