抑肽酶在冠脉搭桥术中的应用及死亡风险

Aprotinin during Coronary-Artery Bypass Grafting and Risk of Death
抑肽酶在冠脉搭桥术中的应用及死亡风险
ABSTRACT
摘要
Background Aprotinin (Trasylol) is used to mitigate bleeding during coronary-artery bypass grafting (CABG). Accumulating evidence suggests that this practice increases mortality.
背景：抑肽酶（特斯乐）被用于冠脉搭桥术中以减少出血。越来越多的证据显示这一治疗方式增加死亡率。
Methods Using 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.
方法：采用Premier Perspective Comparative数据库的电子资料，我们研究了住院病人接受冠脉搭桥当天在手术室应用抑肽酶的33517例患者和应用6-氨基已酸的44682例患者。我们计算了患者死亡出院的数量，并采用三种分析方法：多因素Logistic回归分析（主要分析）；采用倾向得分匹配法分析一个高选择亚组，该组患者接受了足量的研究药物，主刀医生在研究期间进行了50例及以上的冠脉搭桥手术，在入院3天及以后接受手术因此可获得10个以上协同变量的数据；采用工具变量法分析主刀医生对一种或两种药物有偏好的患者的数据。
Results In 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.
结果：33517例接受抑肽酶治疗的患者中1512例（4.5％）患者死亡，44682例接受6-氨基已酸的患者中1101例（2.5%）例患者死亡。在校正了41个患者及医院变量后，抑肽酶组比6-氨基已酸组患者死亡的风险高64％（相对危险度1.64，95％CI，1.50 - 1.78）。在前7天，抑肽酶组院内死亡的相对危险度为1.78（95% CI, 1.56 -2.02）。采用倾向得分匹配法分析的相对危险度为1.32（95% CI, 1.08 - 1.63）。采用工具变量法分析，应用抑肽酶对每100例患者中增加1.59例患者死亡（95% CI, 0.14 - 3.04）。接受抑肽酶的患者术后在血管化和透析的发生率高于接受6-氨基已酸的患者。
Conclusions Patients 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.
结论：在冠脉搭桥当天仅接受抑肽酶治疗的患者比仅接受6-氨基已酸的患者有较高的死亡率。患者和外科医生的特点不那个解释这一差异，在采用多种控制混杂因素的方法后仍然如此。