Mangano Dennis T, Miao Yinghui, Vuylsteke Alain, Tudor Iulia C, Juneja Rajiv, Filipescu Daniela, Hoeft Andreas, Fontes Manuel L, Hillel Zak, Ott Elisabeth, Titov Tatiana, Dietzel Cynthia, Levin Jack
Ischemia Research and Education Foundation, San Bruno, Calif 94066 , USA.
JAMA. 2007 Feb 7;297(5):471-9. doi: 10.1001/jama.297.5.471.
Acute safety concerns have been raised recently regarding certain hemorrhage-sparing medications commonly used in cardiac surgery. However, no comprehensive data exist regarding their associations with long-term mortality.
To contrast long-term all-cause mortality in patients undergoing coronary artery bypass graft (CABG) surgery according to use of 2 lysine analog antifibrinolytics (aminocaproic acid and tranexamic acid), the serine protease inhibitor aprotinin, or no antibleeding agent.
DESIGN, SETTING, AND PARTICIPANTS: Observational study of mortality conducted between November 11, 1996, and December 7, 2006. Following index hospitalization (4374 patients; 69 medical centers), survival was prospectively assessed at 6 weeks, 6 months, and annually for 5 years after CABG surgery among 3876 patients enrolled in a 62-center international cohort study. The associations of survival with hemorrhage-sparing medications were compared using multivariable analyses including propensity adjustments.
Death (all-cause) over 5 years.
Aprotinin treatment (223 deaths among 1072 patients [20.8% 5-year mortality]) was associated with significantly increased mortality compared with control (128 deaths among 1009 patients [12.7%]; covariate adjusted hazard ratio for death, 1.48; 95% confidence interval, 1.19-1.85), whereas neither aminocaproic acid (132 deaths among 834 patients [15.8%]; adjusted hazard ratio for death, 1.03; 95% confidence interval, 0.80-1.33) nor tranexamic acid (65 deaths among 442 patients [14.7%]; adjusted hazard ratio for death, 1.07; 95% confidence interval, 0.80-1.45) was associated with increased mortality. In multivariable logistic regression, either with propensity adjustment or without, aprotinin was independently predictive of 5-year mortality (adjusted odds ratio with propensity adjustment, 1.48; 95% confidence interval, 1.13-1.93; P = .005) among patients with diverse risk profiles, as well as among those surviving their index hospitalization. Neither aminocaproic nor tranexamic acid was associated with increased risk of death.
These findings indicate that in addition to the previously reported acute renal and vascular safety concerns, aprotinin use is associated with an increased risk of long-term mortality following CABG surgery. Use of aprotinin among patients undergoing CABG surgery does not appear prudent because safer and less expensive alternatives (ie, aminocaproic acid and tranexamic acid) are available.
近期，人们对心脏手术中常用的某些减少出血药物提出了急性安全性担忧。然而，关于它们与长期死亡率的关联，尚无全面的数据。
对比接受冠状动脉旁路移植术（CABG）的患者使用两种赖氨酸类似物抗纤溶药物（氨基己酸和氨甲环酸）、丝氨酸蛋白酶抑制剂抑肽酶或不使用抗出血药物后的长期全因死亡率。
设计、地点和参与者：1996年11月11日至2006年12月7日进行的死亡率观察性研究。在首次住院后（4374例患者；69个医疗中心），对参与一项62中心国际队列研究的3876例患者在CABG手术后6周、6个月及每年进行为期5年的前瞻性生存评估。使用包括倾向调整的多变量分析比较生存与减少出血药物的关联。
5年内的死亡（全因）。
与对照组相比，抑肽酶治疗（1072例患者中有223例死亡[5年死亡率20.8%]）与死亡率显著增加相关（1009例患者中有128例死亡[12.7%]；死亡的协变量调整风险比，1.48；95%置信区间，1.19 - 1.85），而氨基己酸（834例患者中有132例死亡[15.8%]；死亡的调整风险比，1.03；95%置信区间，0.80 - 1.33）和氨甲环酸（442例患者中有65例死亡[14.7%]；死亡的调整风险比，1.07；95%置信区间，0.80 - 1.45）均与死亡率增加无关。在多变量逻辑回归中，无论有无倾向调整，抑肽酶在不同风险特征的患者以及首次住院存活的患者中均独立预测5年死亡率（倾向调整后的调整比值比，1.48；95%置信区间，1.13 - 1.93；P = 0.005）。氨基己酸和氨甲环酸均与死亡风险增加无关。
这些发现表明，除了先前报道的急性肾和血管安全性担忧外，使用抑肽酶还与CABG手术后长期死亡率增加的风险相关。在接受CABG手术的患者中使用抑肽酶似乎并不谨慎，因为有更安全且成本更低的替代药物（即氨基己酸和氨甲环酸）可供选择。
