NEJM:低剂量氨甲喋呤能否预防动脉粥样硬化性事件?

2018-12-17 王淳 环球医学

2018年11月,美国和加拿大学者发表在《N Engl J Med》的一项研究,考察了低剂量氨甲喋呤预防动脉粥样硬化性事件的效果。

2018年11月,美国和加拿大学者发表在《N Engl J Med》的一项研究,考察了低剂量氨甲喋呤预防动脉粥样硬化性事件的效果。

背景:炎症与动脉粥样硬化性血栓形成具有因果关系。卡纳单抗是一种可通过中和白细胞介素-1β而抑制炎症的单克隆抗体。既往随机试验显示,与安慰剂相比,其可造成较低的血管事件发生率。本研究旨在确定低剂量氨甲蝶呤的替代炎症抑制方法是否会提供相似的获益。

方法:研究者进行了一项低剂量氨甲蝶呤(目标剂量为15~20mg/周)或配对安慰剂的随机双盲试验,试验对象为4786名既往心肌梗死或多支冠状动脉疾病患者,这些患者额外合并2型糖尿病代谢综合征。所有参与者每天接受叶酸1mg。试验开始时的首要终点为非致命性心肌梗死、非致命性卒中血管死亡的复合。试验将要得出结论但揭盲前,将可导致紧急血运重建的不稳定型心绞痛住院添加到首要终点中。

结果:中位随访2.3年后停止试验。氨甲蝶呤未比安慰剂造成更低的白细胞介素-1β、白细胞介素-6或C反应蛋白水平。氨甲蝶呤组和安慰剂组分别有201和207名患者发生最终的首要终点(发病率比,4.13 vs 4.31/100人-年;风险比[HR],0.96;95% 置信区间[CI],0.79~1.16)。氨甲蝶呤组和安慰剂组分别有170和167名患者发生原始首要终点(发病率比,3.46 vs 3.43/100人-年;HR,1.01;95% CI,0.82~1.25)。与安慰剂相比,氨甲蝶呤与肝酶水平升高、白细胞计数和红细胞压积水平降低、非基底细胞皮肤癌发病率的增加相关。

结论:稳定动脉粥样硬化患者中,与安慰剂相比,低剂量氨甲蝶呤不会降低白细胞介素-1β、白细胞介素-6或C反应蛋白水平,不会造成心血管事件的降低。

原始出处

Ridker PM, Everett BM, Pradhan A, et al. Low-Dose Methotrexate for the Prevention of Atherosclerotic Events. N Engl J Med. 2018 Nov 10. doi: 10.1056/NEJMoa1809798.

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