Population Health Research Institute, Hamilton, ON, Canada.
Department of Medicine, McMaster University, Hamilton, ON, Canada.
EuroIntervention. 2022 Dec 2;18(11):e888-e896. doi: 10.4244/EIJ-D-22-00735.
In patients with ST-segment elevation myocardial infarction (STEMI), early initiation of high-intensity statin therapy, regardless of low-density lipoprotein (LDL) cholesterol levels, is the standard of practice worldwide. Aims: We sought to determine the effect of a similar early initiation strategy, using a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor added to the high-intensity statin, on LDL cholesterol in acute STEMI.
In a randomised, double-blind trial we assigned 68 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) to early treatment with alirocumab 150 mg subcutaneously or to a matching sham control. The first injection was given before primary PCI regardless of the baseline LDL level, then at 2 and 4 weeks. The primary outcome was the percent reduction in direct LDL cholesterol up to 6 weeks, analysed using a linear mixed model. Results: High-intensity statin use was 97% and 100% in the alirocumab and sham-control groups, respectively. At a median of 45 days, the primary outcome of LDL cholesterol decreased by 72.9% with alirocumab (2.97 mmol/L to 0.75 mmol/L) versus 48.1% with the sham control (2.87 mmol/L to 1.30 mmol/L), for a mean between-group difference of -22.3% (p<0.001). More patients achieved the European Society of Cardiology/European Atherosclerosis Society dyslipidaemia guideline target of LDL ≤1.4 mmol/L in the alirocumab group (92.1% vs 56.7%; p<0.001). Within the first 24 hours, LDL declined slightly more rapidly in the alirocumab group than in the sham-control group (-0.01 mmol/L/hour; p=0.03) with similar between-group mean values. Conclusions: In this randomised trial of routine early initiation of PCSK9 inhibitors in patients undergoing primary PCI for STEMI, alirocumab reduced LDL cholesterol by 22% compared with sham control on a background of high-intensity statin therapy. A large trial is needed to determine if this simplified approach followed by long-term therapy improves cardiovascular outcomes in patients with acute STEMI. (ClinicalTrials.gov: NCT03718286).
在 ST 段抬高型心肌梗死（STEMI）患者中，无论低密度脂蛋白（LDL）胆固醇水平如何，早期开始高强度他汀类药物治疗都是全球的标准治疗方法。目的：我们旨在确定使用前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9（PCSK9）抑制剂早期添加到高强度他汀类药物中治疗急性 STEMI 的类似起始策略对 LDL 胆固醇的影响。
在一项随机、双盲试验中，我们将 68 名接受经皮冠状动脉介入治疗（PCI）的 STEMI 患者随机分为早期皮下注射阿利西尤单抗 150mg 或匹配的假对照治疗组。无论基线 LDL 水平如何，第一次注射都在 PCI 前进行，然后在 2 周和 4 周时进行。主要终点是 6 周内直接 LDL 胆固醇的百分比降低，使用线性混合模型进行分析。结果：阿利西尤单抗组和假对照治疗组高强度他汀类药物的使用率分别为 97%和 100%。中位时间为 45 天时，与假对照治疗组（2.87mmol/L 降至 1.30mmol/L）相比，阿利西尤单抗组 LDL 胆固醇的主要终点降低了 72.9%（2.97mmol/L 降至 0.75mmol/L），平均组间差异为-22.3%（p<0.001）。阿利西尤单抗组达到欧洲心脏病学会/欧洲动脉粥样硬化学会血脂异常指南 LDL≤1.4mmol/L 目标的患者比例（92.1% vs 56.7%；p<0.001）高于假对照治疗组。在最初的 24 小时内，与假对照治疗组相比，阿利西尤单抗组 LDL 下降速度略快（-0.01mmol/L/小时；p=0.03），两组之间的平均 LDL 下降值相似。结论：在这项随机试验中，在接受 STEMI 经皮冠状动脉介入治疗的患者中常规早期开始使用 PCSK9 抑制剂，与高强度他汀类药物治疗相比，阿利西尤单抗使 LDL 胆固醇降低了 22%。需要进行大规模试验来确定这种简化方法随后进行长期治疗是否能改善急性 STEMI 患者的心血管结局。（ClinicalTrials.gov：NCT03718286）。
