Aprotinin during coronary-artery bypass grafting and risk of death
Aprotinin during coronary-artery bypass grafting and risk of death
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DOI：
10.1056/nejmoa0707571
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发表时间：
2008-02-21
影响因子：
158.5
通讯作者：
Walker, Alexander M.
中科院分区：
文献类型：
--
作者：
Schneeweiss, Sebastian;Seeger, John D.;Walker, Alexander M.
抑肽酶(Trasylol)用于减少冠状动脉旁路移植术(CABG)中的出血。越来越多的证据表明，这种做法增加了死亡率。方法利用Premier透视比较数据库的电子管理记录，我们研究了在CABG当天使用抑肽酶(33517例)或氨基己酸(44682例)的住院患者的手术室费用。我们列出了出院死亡患者的数量，并进行了三种类型的分析：多变量Logistic回归分析(初级分析)；在高度精选的子队列中，接受全量研究药物的患者、在研究期间进行了50次或更多CABG手术的外科医生进行CABG的患者的倾向-得分匹配，以及由于手术发生在第3天或更晚的患者的10个额外协变量的信息；结果33,517名抑肽酶接受者中有1512人(4.5%)死亡，44,682名氨基己酸者中有1101人(2.5%)死亡。在调整了患者和医院的41个特征后，抑肽酶组的估计死亡风险比氨基己酸组高%(相对危险度为1.64；95%可信区间[CI]为1.5~1.78)。术后前7天，抑肽酶组住院死亡的调整相对危险度为1.78(95%CI，1.56比2.02)。倾向得分匹配分析的相对危险度为1.32(95%可信区间为1.08~1.63)。在工具变量分析中，抑肽酶的使用被发现与每100名患者1.59的额外死亡风险相关(95%CI，0.14至3.04)。在接受抑肽酶的患者中，术后血管重建和透析的发生率高于接受氨基己酸的患者。结论冠状动脉旁路移植术当天单独应用抑肽酶的患者的死亡率高于单独接受氨基己酸的患者。患者和外科医生的特点都不能解释这种差异，这种差异通过几种方法来控制混淆。
BackgroundAprotinin (Trasylol) is used to mitigate bleeding during coronary-artery bypass grafting (CABG). Accumulating evidence suggests that this practice increases mortality.MethodsUsing electronic administrative records of the Premier Perspective Comparative Database, we studied hospitalized patients with operating-room charges for the use of aprotinin (33,517 patients) or aminocaproic acid (44,682 patients) on the day CABG was performed. We tabulated the numbers of patients with a hospital-discharge status of death and performed three types of analyses: a multivariable logistic-regression analysis (primary analysis); propensity-score matching in the highly selected subcohort of patients who received full amounts of the study drug, who underwent CABG by surgeons who performed 50 or more CABG surgeries during the study period, and for whom information on 10 additional covariates was available because the surgery occurred on hospital day 3 or later; and an instrumental-variable analysis of data from patients whose surgeons showed a strong preference for one of the two study drugs.ResultsIn all, 1512 of the 33,517 aprotinin recipients (4.5%) and 1101 of the 44,682 aminocaproic acid recipients (2.5%) died. After adjustment for 41 characteristics of patients and hospitals, the estimated risk of death was 64% higher in the aprotinin group than in the aminocaproic acid group (relative risk, 1.64; 95% confidence interval [CI], 1.50 to 1.78). In the first 7 days after surgery, the adjusted relative risk of in-hospital death in the aprotinin group was 1.78 (95% CI, 1.56 to 2.02). The relative risk in a propensity-score-matched analysis was 1.32 (95% CI, 1.08 to 1.63). In the instrumental-variable analysis, the use of aprotinin was found to be associated with an excess risk of death of 1.59 per 100 patients (95% CI, 0.14 to 3.04). Postoperative revascularization and dialysis were more frequent among recipients of aprotinin than among recipients of aminocaproic acid.ConclusionsPatients who received aprotinin alone on the day of CABG surgery had a higher mortality than patients who received aminocaproic acid alone. Characteristics of neither the patients nor the surgeons explain the difference, which persisted through several approaches to control confounding.