Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia; The Department of Vascular and Endovascular Surgery, The Townsville University Hospital, Townsville, Queensland, Australia; The Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia.
The Department of Vascular and Endovascular Surgery, The Townsville University Hospital, Townsville, Queensland, Australia.
Ann Vasc Surg. 2022 Jan;78:310-320. doi: 10.1016/j.avsg.2021.07.010. Epub 2021 Sep 16.
Immune activation is strongly implicated in atherosclerotic plaque instability, however, the effect of immunosuppressant drugs on cardiovascular events in patients with peripheral artery disease (PAD) is not known. The aim of this study was to assess whether prescription of one or more immune suppressant drugs was associated with a lower risk of major adverse cardiovascular (MACE; i.e. myocardial infarction, stroke or cardiovascular events) or limb events (MALE; i.e. major amputation or requirement for peripheral revascularization) in patients with PAD.
A total of 1506 participants with intermittent claudication (n = 872) or chronic limb threatening ischemia (CLTI; n = 634) of whom 53 (3.5%) were prescribed one or more immunosuppressant drugs (prednisolone 41; methotrexate 17; leflunomide 5; hydroxychloroquine 3; azathioprine 2; tocilizumab 2; mycophenolate 1; sulfasalazine 1; adalimumab 1) were recruited from 3 Australian hospitals. Participants were followed for a median of 3.9 (inter-quartile range 1.2, 7.3) years. The association of immunosuppressant drug prescription with MACE or MALE was examined using Cox proportional hazard analyses.
After adjusting for other risk factors, prescription of an immunosuppressant drug was associated with a significantly greater risk of MACE (Hazard ratio, HR, 1.83, 95% confidence intervals, CI, 1.11, 3.01; P = 0.017) but not MALE (HR 1.32, 95% CI 0.90, 1.92; P = 0.153). In a sub-analysis restricted to participants with CLTI findings were similar: MACE (HR 2.44, 95% CI 1.32, 4.51; P = 0.005); MALE (HR 1.38, 95% CI 0.87, 2.19; P = 0.175); major amputation (HR 1.37, 95% CI 0.49, 3.86; P = 0.547).
This cohort study suggested that immunosuppressant drug therapy is associated with a greater risk of MACE amongst patients with PAD.
免疫激活强烈提示动脉粥样硬化斑块不稳定，但免疫抑制剂药物对周围动脉疾病（PAD）患者心血管事件的影响尚不清楚。本研究旨在评估在 PAD 患者中，一种或多种免疫抑制剂药物的处方是否与主要不良心血管（MACE；即心肌梗死、中风或心血管事件）或肢体事件（MALE；即大截肢或需要外周血运重建）的风险降低相关。
共有 1506 名间歇性跛行（n=872）或慢性肢体威胁性缺血（CLTI；n=634）患者参加了这项研究，其中 53 名（3.5%）患者服用了一种或多种免疫抑制剂药物（泼尼松龙 41 例；甲氨蝶呤 17 例；来氟米特 5 例；羟氯喹 3 例；硫唑嘌呤 2 例；托珠单抗 2 例；霉酚酸酯 1 例；柳氮磺胺吡啶 1 例；阿达木单抗 1 例），他们均来自澳大利亚的 3 家医院。中位随访时间为 3.9 年（四分位距 1.2 年，7.3 年）。使用 Cox 比例风险分析评估免疫抑制剂药物处方与 MACE 或 MALE 的相关性。
在调整其他危险因素后，免疫抑制剂药物的处方与 MACE 的风险显著增加相关（风险比，HR，1.83，95%置信区间，CI，1.11，3.01；P=0.017），但与 MALE 无关（HR 1.32，95%CI 0.90，1.92；P=0.153）。在一项仅限于 CLTI 参与者的亚分析中，结果相似：MACE（HR 2.44，95%CI 1.32，4.51；P=0.005）；MALE（HR 1.38，95%CI 0.87，2.19；P=0.175）；大截肢（HR 1.37，95%CI 0.49，3.86；P=0.547）。
这项队列研究表明，PAD 患者的免疫抑制剂治疗与 MACE 风险增加相关。
