Jones Douglas W, Schermerhorn Marc L, Brooke Benjamin S, Conrad Mark F, Goodney Philip P, Wyers Mark C, Stone David H
Department of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, Mass.
Section of Vascular Surgery, The University of Utah School of Medicine, Salt Lake City, Utah.
J Vasc Surg. 2017 Jun;65(6):1719-1728.e1. doi: 10.1016/j.jvs.2016.12.102. Epub 2017 Feb 20.
Controversy persists surrounding the perceived bleeding risk associated with perioperative clopidogrel use in patients undergoing lower extremity bypass (LEB). The purpose of this study was to examine the LEB bleeding risk and clinical sequelae associated with clopidogrel.
All LEBs in the Vascular Quality Initiative (VQI) from 2008 to 2014 were studied. The exposure was perioperative clopidogrel. Primary outcomes were blood transfusion, estimated blood loss ≥500 mL, and reoperation for bleeding. Secondary outcomes included mean operative time, major cardiac events, respiratory complications, infectious complications, and in-hospital mortality. Univariate and multivariable analyses were used to analyze patients on the basis of clopidogrel use and its association with outcomes. Nonparametric test for trend and Mantel-Haenszel methods were used to analyze association of clopidogrel use with blood transfusion and secondary outcomes.
Among the LEB cohort (N = 9179), 28% (n = 2544) were taking clopidogrel and 72% (n = 6635) were not. Patients taking clopidogrel were more likely to have coronary disease, prior coronary intervention, abnormal findings on stress test, and aspirin use (P < .001 for all). Patients taking clopidogrel were more likely to receive blood transfusion (38% vs 24%; P < .001) and to have estimated blood loss ≥500 mL (21% vs 12%; P < .001). Reoperation for bleeding rates were similar (0.9% vs 1.1%; P = .9). Clopidogrel use was also associated with increased mean operative times (244 minutes vs 232 minutes; P < .001) as well as with cardiac complications (8.8% vs 6.5%; P = .001), respiratory complications (2.5% vs 1.6%; P = .007), and in-hospital mortality (1.3% vs 0.8%; P = .03). Multivariable analysis demonstrated that clopidogrel was associated with increased risk of 1- or 2-unit blood transfusion (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.5-2.1; P < .001) and >2-unit blood transfusion (OR, 2.0; 95% CI, 1.7-2.5; P < .001). Major cardiac events (OR, 1.2; 95% CI, 1.0-1.5; P = .05) and respiratory complications (OR, 1.4; 95% CI, 1.0-2.0; P = .03) were also independently associated with clopidogrel use. Weighted Mantel-Haenszel ORs controlling for blood transfusion amount revealed no remaining effect of clopidogrel on major cardiac events (OR, 1.1; P = .4) or respiratory complications (OR, 1.0; P = .8).
Perioperative clopidogrel use in LEB surgery is associated with increased blood loss and blood transfusion. Associated clinical sequelae include increased cardiac and pulmonary complications. Accordingly, surgeons should consider discontinuation of perioperative clopidogrel when it is clinically appropriate unless it is strongly indicated at the time of LEB.
在接受下肢旁路移植术（LEB）的患者中，围手术期使用氯吡格雷所带来的出血风险仍存在争议。本研究旨在探讨与氯吡格雷相关的LEB出血风险及临床后果。
对2008年至2014年血管质量改进计划（VQI）中的所有LEB病例进行研究。暴露因素为围手术期使用氯吡格雷。主要结局为输血、估计失血量≥500 mL以及因出血而再次手术。次要结局包括平均手术时间、重大心脏事件、呼吸并发症、感染性并发症及住院死亡率。采用单因素和多因素分析，根据氯吡格雷的使用情况及其与结局的关联对患者进行分析。使用非参数趋势检验和Mantel-Haenszel方法分析氯吡格雷使用与输血及次要结局的关联。
在LEB队列（N = 9179）中，28%（n = 2544）的患者正在服用氯吡格雷，72%（n = 6635）的患者未服用。服用氯吡格雷的患者更易患冠状动脉疾病、既往有冠状动脉介入治疗史、运动试验结果异常且使用阿司匹林（所有P <.001）。服用氯吡格雷的患者更易接受输血（38%对24%；P <.001）且估计失血量≥500 mL（21%对12%；P <.001）。因出血而再次手术的发生率相似（0.9%对1.1%；P =.9）。使用氯吡格雷还与平均手术时间延长（244分钟对232分钟；P <.001）以及心脏并发症（8.8%对6.5%；P =.001）、呼吸并发症（2.5%对1.6%；P =.007）和住院死亡率（1.3%对0.8%；P =.03）增加相关。多因素分析表明，氯吡格雷与1或2单位输血风险增加相关（比值比[OR]，1.8；95%置信区间[CI]，1.5 - 2.1；P <.001）以及>2单位输血风险增加相关（OR，2.0；95% CI，1.7 - 2.5；P <.001）。重大心脏事件（OR，1.2；95% CI，1.0 - 1.5；P =.05）和呼吸并发症（OR，1.4；95% CI，1.0 - 2.0；P =.03）也与氯吡格雷的使用独立相关。控制输血量的加权Mantel-Haenszel ORs显示，氯吡格雷对重大心脏事件（OR，1.1；P =.4）或呼吸并发症（OR，1.0；P =.8）无残留影响。
LEB手术围手术期使用氯吡格雷与失血量和输血增加相关。相关的临床后果包括心脏和肺部并发症增加。因此，除非在LEB时强烈指征使用，否则外科医生在临床适当时应考虑停用围手术期氯吡格雷。
