Mangano Dennis T, Tudor Iulia C, Dietzel Cynthia
Ischemia Research and Education Foundation, San Bruno, Calif 94066, USA.
N Engl J Med. 2006 Jan 26;354(4):353-65. doi: 10.1056/NEJMoa051379.
The majority of patients undergoing surgical treatment for ST-elevation myocardial infarction receive antifibrinolytic therapy to limit blood loss. This approach appears counterintuitive to the accepted medical treatment of the same condition--namely, fibrinolysis to limit thrombosis. Despite this concern, no independent, large-scale safety assessment has been undertaken.
In this observational study involving 4374 patients undergoing revascularization, we prospectively assessed three agents (aprotinin [1295 patients], aminocaproic acid [883], and tranexamic acid [822]) as compared with no agent (1374 patients) with regard to serious outcomes by propensity and multivariable methods. (Although aprotinin is a serine protease inhibitor, here we use the term antifibrinolytic therapy to include all three agents.)
In propensity-adjusted, multivariable logistic regression (C-index, 0.72), use of aprotinin was associated with a doubling in the risk of renal failure requiring dialysis among patients undergoing complex coronary-artery surgery (odds ratio, 2.59; 95 percent confidence interval, 1.36 to 4.95) or primary surgery (odds ratio, 2.34; 95 percent confidence interval, 1.27 to 4.31). Similarly, use of aprotinin in the latter group was associated with a 55 percent increase in the risk of myocardial infarction or heart failure (P<0.001) and a 181 percent increase in the risk of stroke or encephalopathy (P=0.001). Neither aminocaproic acid nor tranexamic acid was associated with an increased risk of renal, cardiac, or cerebral events. Adjustment according to propensity score for the use of any one of the three agents as compared with no agent yielded nearly identical findings. All the agents reduced blood loss.
The association between aprotinin and serious end-organ damage indicates that continued use is not prudent. In contrast, the less expensive generic medications aminocaproic acid and tranexamic acid are safe alternatives.
大多数接受ST段抬高型心肌梗死手术治疗的患者接受抗纤溶治疗以限制失血。这种方法似乎与针对相同病症的公认医学治疗方法（即溶栓以限制血栓形成）背道而驰。尽管存在这种担忧，但尚未进行独立的大规模安全性评估。
在这项涉及4374例接受血运重建的患者的观察性研究中，我们通过倾向和多变量方法前瞻性地评估了三种药物（抑肽酶[1295例患者]、氨基己酸[883例]和氨甲环酸[822例]）与未使用任何药物（1374例患者）相比的严重结局。（尽管抑肽酶是一种丝氨酸蛋白酶抑制剂，但在此我们使用抗纤溶治疗一词来包括所有三种药物。）
在倾向调整的多变量逻辑回归（C指数，0.72）中，使用抑肽酶与接受复杂冠状动脉手术（比值比，2.59；95%置信区间，1.36至4.95）或初次手术（比值比，2.34；95%置信区间，1.27至4.31）的患者中需要透析的肾衰竭风险加倍相关。同样，在后一组中使用抑肽酶与心肌梗死或心力衰竭风险增加55%（P<0.001）以及中风或脑病风险增加181%（P=0.001）相关。氨基己酸和氨甲环酸均与肾脏、心脏或脑部事件风险增加无关。根据使用三种药物中的任何一种与未使用药物的倾向评分进行调整得出了几乎相同的结果。所有药物均减少了失血。
抑肽酶与严重的终末器官损害之间的关联表明继续使用并不谨慎。相比之下，价格较低的非专利药物氨基己酸和氨甲环酸是安全的替代品。
