Department of Cardiology, Sixth Medical Center of Chinese PLA General Hospital, Beijing, 100048, China.
Department of Ultrasound, First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China; The Second Medical College of Lanzhou University, Lanzhou, Gansu, 730030, China.
Atherosclerosis. 2024 Apr;391:117471. doi: 10.1016/j.atherosclerosis.2024.117471. Epub 2024 Feb 13.
BACKGROUND AND AIMS: We aimed to explore the effect of PCSK9 inhibitor based on the background of statin on carotid intraplaque neovascularization (IPN) assessed by serial contrast-enhanced ultrasound (CEUS) analysis in Chinese patients with premature coronary artery disease (PCAD). METHODS: 41 patients were included to receive treatments with biweekly evolocumab (n = 22) or placebo (n = 19) in addition to statin therapy for 52 weeks. All patients were newly diagnosed with PCAD and treatments were initiated at baseline of the observations. Baseline and 52-week CEUS were acquired to measure the max plaque height (MPH) and IPN. The primary outcome was the 52-week IPN changes, the secondary endpoints included the 52-week MPH changes and major adverse cardiovascular events. RESULTS: The mean ± SD age of the participants was 46.76 ± 8.56 years, and 61% (25/41) of patients were on statins before the start of the study. There was no statistically significant difference in the history of statins treatment and the initiated lipid-lowering therapy of atorvastatin and rosuvastatin between groups (p > 0.05). At 52 weeks, the evolocumab group showed a lower LDL level (0.84 ± 0.45 mmol/L vs. 1.58 ± 0.51 mmol/L, p < 0.001) and a greater decrease in percent reduction of LDL-C level (-65% vs. -32%) and a higher percent of achieving lipid-lowering target (95% vs. 53%, p < 0.05) compared with the placebo group. At 52 weeks, IPN (evolocumab group: 0.50 ± 0.60 vs. 1.50 ± 0.80, p < 0.001; placebo group: 0.79 ± 0.54 vs. 1.26 ± 0.65, p < 0.05) and MPH (evolocumab group: 2.01 ± 0.44 mm vs. 2.57 ± 0.90 mm, p < 0.05, placebo group: 2.21 ± 0.58 mm vs. 2.92 ± 0.86 mm, p < 0.05) reduced significantly in both groups from baseline to 52-week follow-up. IPN and MPH were decreased by both treatments. Still, there was no significant difference in delta (52 weeks - baseline) MPH by an ANOVA analysis between the two groups [evolocumab group: -0.56 mm (2.01 mm-2.57 mm); placebo group: -0.71 mm (2.21 mm-2.92 mm), p > 0.05]. In the evolocumab group, the change in the mean reduction of IPN from baseline [-1.00 (0.50-1.50) vs. -0.47 (0.79-1.26), p < 0.05] and the incidence of patients with carotid IPN decrease were significantly greater reduction (90% vs. 58%, p < 0.05). CONCLUSIONS: If compared to placebo, the PCSK9 inhibitor evolocumab combined with statins resulted in a greater decrease in LDL-C and plaque neovascularization in Chinese patients with PCAD.
背景与目的：我们旨在通过连续对比增强超声（CEUS）分析探讨在他汀类药物基础上使用 PCSK9 抑制剂对中国早发冠心病（PCAD）患者颈动脉斑块内新生血管（IPN）的影响。
方法：纳入 41 例患者，在他汀类药物治疗的基础上，每两周接受依洛尤单抗（n=22）或安慰剂（n=19）治疗 52 周。所有患者均为新发 PCAD，在观察的基线开始治疗。获取基线和 52 周的 CEUS 以测量最大斑块高度（MPH）和 IPN。主要结局为 52 周时的 IPN 变化，次要终点包括 52 周时的 MPH 变化和主要不良心血管事件。
结果：参与者的平均年龄为 46.76±8.56 岁，61%（25/41）的患者在研究开始前使用他汀类药物。两组间他汀类药物治疗史和起始降脂治疗阿托伐他汀和瑞舒伐他汀无统计学差异（p>0.05）。52 周时，依洛尤单抗组 LDL 水平较低（0.84±0.45mmol/L 比 1.58±0.51mmol/L，p<0.001），LDL-C 水平降低百分比较大（-65%比-32%），降脂达标百分比较高（95%比 53%，p<0.05）。52 周时，IPN（依洛尤单抗组：0.50±0.60 比 1.50±0.80，p<0.001；安慰剂组：0.79±0.54 比 1.26±0.65，p<0.05）和 MPH（依洛尤单抗组：2.01±0.44mm 比 2.57±0.90mm，p<0.05，安慰剂组：2.21±0.58mm 比 2.92±0.86mm，p<0.05）均显著降低从基线到 52 周随访。两种治疗均降低了 IPN 和 MPH。然而，两组间 ANOVA 分析的 MPH 差值（52 周-基线）无统计学差异[依洛尤单抗组：-0.56mm（2.01mm-2.57mm）；安慰剂组：-0.71mm（2.21mm-2.92mm），p>0.05]。在依洛尤单抗组，从基线开始的 IPN 平均降低幅度的变化[-1.00（0.50-1.50）比-0.47（0.79-1.26），p<0.05]和颈动脉 IPN 减少的患者比例显著更大（90%比 58%，p<0.05）。
结论：与安慰剂相比，PCSK9 抑制剂依洛尤单抗联合他汀类药物可使中国早发冠心病患者的 LDL-C 和斑块新生血管明显减少。
JACC Cardiovasc Imaging. 2022-7
J Am Coll Cardiol. 2018-10-23
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