Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction The PACMAN-AMI Randomized Clinical Trial
Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction The PACMAN-AMI Randomized Clinical Trial
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DOI：
10.1001/jama.2022.5218
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发表时间：
2022-04-03
影响因子：
120.7
通讯作者：
Koskinas, Konstantinos C.
中科院分区：
文献类型：
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作者：
Raber, Lorenz;Ueki, Yasushi;Koskinas, Konstantinos C.
重要性易于破裂并导致不良心脏事件的冠状动脉斑块的特征是斑块负荷大、脂质含量高和纤维帽薄。他汀类药物可以阻止冠状动脉粥样硬化的进展;然而，前蛋白转化酶枯草杆菌蛋白酶kexin 9型抑制剂alirocumab加到他汀类药物治疗中对斑块负荷和组成的影响在很大程度上仍然未知。安慰剂对照、随机临床试验（入组时间：2017年5月9日至2020年10月7日;最终随访时间：2021年10月13日）在9家欧洲学术医院招募了300名因急性心肌梗死接受经皮冠状动脉介入治疗的患者。（150毫克; n = 148）或安慰剂（n = 152），在罪犯病变的紧急经皮冠状动脉介入治疗后24小时内开始，除高强度他汀类药物治疗外，持续52周（瑞舒伐他汀，20 mg）。主要结果和测量血管内超声检查（IVUS），近红外光谱，在基线和52周后对2支非梗死相关冠状动脉连续进行光学相干断层扫描。主要疗效终点是IVUS衍生的动脉粥样硬化体积百分比从基线至第52周的变化。两个把握度次要终点是近红外光谱衍生的最大脂质核心负荷指数在4 mm内的变化（较高的值表明较高的脂质含量）和光学相干断层扫描衍生的最小纤维帽厚度（较小的值表示薄帽、易损斑块）。结果在300例随机分组的患者中，（平均[SD]年龄，58.5 [9.7]岁; 56名[18.7%]女性;平均[SD]低密度脂蛋白胆固醇水平，152.4 [33.8] mg/dL），265名（88.3%）接受了537条动脉的连续IVUS成像。第52周时，alirocumab组动脉粥样硬化体积百分比的平均变化为-2.13%，安慰剂组为-0.92%（差异为-1.21% [95% CI，-1.78%至-0.65%]，P <0.001）。alirocumab组4 mm内最大脂质核心负荷指数的平均变化为-79.42，安慰剂组为-37.60（差异，-41.24 [95% CI，-70.71至-11.77]; P = .006）。alirocumab组最小纤维帽厚度的平均变化为62.67 μ m，安慰剂组为33.19 μ m（差异，29.65 μ m [95% CI，11.75-47.55]; P = 0.001）。在急性心肌梗死患者中，与安慰剂相比，在高强度他汀类药物治疗中加入皮下注射两周一次alirocumab，52周后，非梗死相关动脉中的冠状动脉斑块消退显著增加。需要进一步研究以了解alirocumab是否改善了该人群的临床结局。
IMPORTANCE Coronary plaques that are prone to rupture and cause adverse cardiac events are characterized by large plaque burden, large lipid content, and thin fibrous caps. Statins can halt the progression of coronary atherosclerosis; however, the effect of the proprotein convertase subtilisin kexin type 9 inhibitor alirocumab added to statin therapy on plaque burden and composition remains largely unknown.OBJECTIVE To determine the effects of alirocumab on coronary atherosclerosis using serial multimodality intracoronary imaging in patients with acute myocardial infarction.DESIGN, SETTING, AND PARTICIPANTS The PACMAN-AMI double-blind, placebo-controlled, randomized clinical trial (enrollment: May 9, 2017, through October 7, 2020; final follow-up: October 13, 2021) enrolled 300 patients undergoing percutaneous coronary intervention for acute myocardial infarction at 9 academic European hospitals.INTERVENTIONS Patients were randomized to receive biweekly subcutaneous alirocumab (150 mg; n = 148) or placebo (n = 152), initiated less than 24 hours after urgent percutaneous coronary intervention of the culprit lesion, for 52 weeks in addition to high-intensity statin therapy (rosuvastatin, 20 mg).MAIN OUTCOMES AND MEASURES Intravascular ultrasonography (IVUS), near-infrared spectroscopy, and optical coherence tomography were serially performed in the 2 non-infarct-related coronary arteries at baseline and after 52 weeks. The primary efficacy end point was the change in IVUS-derived percent atheroma volume from baseline to week 52. Two powered secondary end points were changes in near-infrared spectroscopy-derived maximum lipid core burden index within 4 mm (higher values indicating greater lipid content) and optical coherence tomography-derived minimal fibrous cap thickness (smaller values indicating thin-capped, vulnerable plaques) from baseline to week 52.RESULTS Among 300 randomized patients (mean [SD] age, 58.5 [9.7] years; 56 [18.7%) women; mean [SD] low-density lipoprotein cholesterol level, 152.4 [33.8] mg/dL), 265 (88.3%) underwent serial IVUS imaging in 537 arteries. At 52 weeks, mean change in percent atheroma volume was -2.13% with alirocumab vs -0.92% with placebo (difference, -1.21% [95% CI, -1.78% to -0.65%], P < .001). Mean change in maximum lipid core burden index within 4 mm was -79.42 with alirocumab vs -37.60 with placebo (difference, -41.24 [95% CI, -70.71 to -11.77]; P = .006). Mean change in minimal fibrous cap thickness was 62.67 mu m with alirocumab vs 33.19 mu m with placebo (difference, 29.65 mu m [95% Cl, 11.75-47.55]; P = .001). Adverse events occurred in 70.7% of patients treated with alirocumab vs 72.8% of patients receiving placebo.CONCLUSIONS AND RELEVANCE Among patients with acute myocardial infarction, the addition of subcutaneous biweekly alirocumab, compared with placebo, to high-intensity statin therapy resulted in significantly greater coronary plaque regression in non-infarct-related arteries after 52 weeks. Further research is needed to understand whether alirocumab improves clinical outcomes in this population.