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高剂量他汀类药物在体外循环相关手术中的预防作用:临床应用

High dose statin prophylaxis in cardiopulmonary bypass related surgery: clinical utility.

作者信息

Chee Yie Roei, Watson R William G, McCarthy James, Chughtai Jehan Zeb, Nölke Lars, Healy David G

机构信息

Cardiothoracic Surgery, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland.

Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.

出版信息

J Cardiothorac Surg. 2017 Mar 31;12(1):20. doi: 10.1186/s13019-017-0582-8.

Abstract

BACKGROUND

Previous studies from our group demonstrated the anti-inflammatory properties of statins on cardiopulmonary bypass (CPB), through inhibition of neutrophil transendothelial migration. We sought to determine the utility of preoperative statin on patients undergoing cardiac surgery, to investigate any moderating effects on the systemic inflammatory response (SIRS) with CPB, and to evaluate any clinical impact on our patients.

METHODS

This is a prospective, randomised controlled trial with national regulatory body approval. Eligible patients were already on oral statin therapy. They were then randomly assigned to either investigation arm (n = 15, atorvastatin 80 mg for 2 weeks before surgery) or control arm (n = 15, no change to current statin therapy). Blood and urine samples were collected at 3 timepoints. Postoperative clinical measures were documented.

RESULTS

Patients in the investigation arm have significantly lower troponin level (p = 0.016), and lower level of urine neutrophil gelatinase-associated lipocalin (NGAL; p = 0.002); thus demonstrating a lesser degree of cardiac and renal injury in these patients. Higher level of Interleukin-8 (IL-8) at baseline (p = 0.036) and 4 h post cross-clamp removal (p = 0.035) in the investiation arm. A similar trend is also observed in Matrix Metalloproteinase-9 (MMP-9; p > 0.05). There were however no differences in clinical outcomes.

CONCLUSIONS

Maximizing the dose of statin in patients waiting for cardiac surgery has measurable biological effects. There is evidence of less cardiac and renal damage. The use of preoperative statins and in particular, high dose preoperative statin therapy, may prove a useful new tool for optimal preparation of patients for cardiac surgery.

TRIAL REGISTRATION

EudraCT no. 2012-003396-20 . Registered 05 November 2012.

摘要

背景

我们团队之前的研究表明,他汀类药物通过抑制中性粒细胞跨内皮迁移,对体外循环(CPB)具有抗炎特性。我们试图确定术前使用他汀类药物对接受心脏手术患者的效用,研究其对CPB引起的全身炎症反应(SIRS)的任何调节作用,并评估对我们患者的任何临床影响。

方法

这是一项经国家监管机构批准的前瞻性随机对照试验。符合条件的患者已在接受口服他汀类药物治疗。然后将他们随机分配到研究组(n = 15,术前2周服用阿托伐他汀80毫克)或对照组(n = 15,当前他汀类药物治疗不变)。在3个时间点采集血液和尿液样本。记录术后临床指标。

结果

研究组患者的肌钙蛋白水平显著较低(p = 0.016),尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平较低(p = 0.002);因此表明这些患者的心脏和肾脏损伤程度较轻。研究组在基线时(p = 0.036)和松开主动脉阻断钳后4小时(p = 0.035)白细胞介素-8(IL-8)水平较高。基质金属蛋白酶-9(MMP-9)也观察到类似趋势(p>0.05)。然而,临床结局并无差异。

结论

在等待心脏手术的患者中最大化他汀类药物剂量具有可测量的生物学效应。有证据表明心脏和肾脏损伤较少。术前使用他汀类药物,特别是高剂量术前他汀类药物治疗,可能是为心脏手术患者进行最佳准备的一种有用新工具。

试验注册

欧洲药品管理局临床试验编号2012-003396-20。于2012年11月5日注册。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b795/5374690/57d872bb5fb3/13019_2017_582_Fig1_HTML.jpg

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