依洛尤单抗治疗下斑块负荷逆转与冠状动脉粥样硬化特征：ARCHITECT 研究。
Characteristics of Coronary Atherosclerosis Related to Plaque Burden Regression During Treatment With Alirocumab: The ARCHITECT Study.
机构信息
Cardiology Department, Clinico San Carlos University Hospital, Madrid, Spain (L.P.d.I.).
Internal Medicine Department, Hospital Abente y Lago, A Coruña, Spain (J.L.D.-D.).
出版信息
Circ Cardiovasc Imaging. 2024 Jan;17(1):e016206. doi: 10.1161/CIRCIMAGING.123.016206. Epub 2024 Jan 11.
BACKGROUND
Intensive lipid-lowering therapy may induce coronary atherosclerosis regression. Nevertheless, the factors underlying the effect of lipid-lowering therapy on disease regression remain poorly characterized. Our aim was to determine which characteristics of atherosclerotic plaque are associated with a greater reduction in coronary plaque burden (PB) after treatment with alirocumab in patients with familial hypercholesterolemia.
METHODS
The ARCHITECT study (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) is a phase IV, open-label, multicenter, single-arm clinical trial to assess the effect of the treatment with alirocumab for 78 weeks on the coronary atherosclerotic PB and its characteristics in subjects with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent a coronary computed tomographic angiography at baseline and a final one at 78 weeks. Every patient received alirocumab 150 mg subcutaneously every 14 days in addition to high-intensity statin therapy.
RESULTS
One hundred and four patients were enrolled. Median age was 53.3 (46.2-59.4) years and 54 were women (51.9%). The global coronary PB changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up, which is -4.6% (-7.7% to -1.9%; <0.001) reduction. A decrease in the percentage of unstable core (fibro-fatty+necrotic plaque; from 14.1 [7.9-22.3] to 8.0 [6.4-10.6]; -6.6%; <0.001) was found. A greater PB (β, 0.36 [0.13-0.59]; =0.002) and a higher proportion of unstable core (β, 0.15 [0.08-0.22]; <0.001) were significantly related to PB regression.
CONCLUSIONS
Treatment with alirocumab in addition to high-intensity statin therapy might produce a greater PB regression in patients with familial hypercholesterolemia with higher baseline PB and in those with larger unstable core. Further studies are needed to corroborate the hypothesis raised by these results.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique identifier: NCT05465278.
背景
强化降脂治疗可能会诱导冠状动脉粥样硬化消退。然而，降脂治疗对疾病消退影响的机制仍未得到充分描述。我们的目的是确定在家族性高胆固醇血症患者中，使用阿利西尤单抗治疗后，哪些斑块特征与冠状动脉斑块负荷（PB）的更大减少相关。
方法
ARCHITECT 研究（阿利西尤单抗对动脉粥样硬化斑块体积、结构和组成的影响）是一项 IV 期、开放标签、多中心、单臂临床试验，旨在评估阿利西尤单抗治疗 78 周对家族性高胆固醇血症患者冠状动脉粥样硬化 PB 及其特征的影响，这些患者无临床动脉粥样硬化性心血管疾病。参与者在基线和 78 周时进行冠状动脉计算机断层扫描血管造影。每位患者在高强度他汀类药物治疗的基础上加用皮下注射阿利西尤单抗 150mg，每 14 天一次。
结果
共纳入 104 例患者。中位年龄为 53.3（46.2-59.4）岁，54 例为女性（51.9%）。总的冠状动脉 PB 从入组时的 34.6%（32.5%-36.8%）降至随访时的 30.4%（27.4%-33.4%），减少了 4.6%（-7.7%至-1.9%；<0.001）。不稳定核心（纤维脂肪+坏死斑块）的比例也有所下降（从 14.1%（7.9%-22.3%）降至 8.0%（6.4%-10.6%）；-6.6%；<0.001）。更大的 PB（β，0.36 [0.13-0.59]；=0.002）和更高比例的不稳定核心（β，0.15 [0.08-0.22]；<0.001）与 PB 消退显著相关。
结论
在高强度他汀类药物治疗的基础上加用阿利西尤单抗治疗可能会使基线 PB 较高和不稳定核心较大的家族性高胆固醇血症患者的 PB 更大程度地消退。需要进一步的研究来证实这些结果所提出的假设。
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