Gagne Joshua J, Griesdale Donald E G, Schneeweiss Sebastian
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02120, USA.
Pharmacoepidemiol Drug Saf. 2009 Apr;18(4):259-68. doi: 10.1002/pds.1714.
Observational studies have reported conflicting results regarding aprotinin's risk of renal dysfunction and death. A meta-analysis was conducted to summarize results and explain variation of published epidemiologic studies on risks of renal dysfunction and death associated with aprotinin.
MEDLINE and EMBASE were systematically searched for non-experimental studies that reported risk of renal dysfunction or death with aprotinin use during cardiac surgery in adults. Random-effects meta-analyses were used to pool results across studies for each outcome. Stratified and meta-regression analyses were used to identify sources of heterogeneity.
Eleven relevant studies were identified and included in the analysis, including 10 that reported renal dysfunction and seven that reported death. Aprotinin was associated with renal dysfunction (risk ratio (RR), 1.42; 95%CI 1.13-1.79) and long-term mortality (hazard ratio (HR) 1.22; 95%CI 1.08-1.39). Pooled estimates were lower for short-term mortality (RR 1.16; 95%CI 0.84-1.58) and renal failure requiring dialysis (RR 1.17; 95%CI 0.99-1.38). Cardiopulmonary bypass (CPB) time, which may be on the causal pathway, was a significant source of heterogeneity, with a 29% increased risk of renal dysfunction for every 10 minute increase in CPB time (p = 0.03).
Despite some studies that reported no association between aprotinin and renal outcomes during cardiac surgery, the totality of epidemiologic evidence indicates an increased risk that cannot be fully explained by need for transfused red blood cells (RBCs). Epidemiologic studies also suggest an increased risk of long-term mortality associated with aprotinin as compared to various comparators used in these studies, although residual confounding cannot be ruled out.
观察性研究报告了关于抑肽酶导致肾功能障碍和死亡风险的相互矛盾的结果。进行了一项荟萃分析，以总结结果并解释已发表的关于抑肽酶相关肾功能障碍和死亡风险的流行病学研究的差异。
系统检索MEDLINE和EMBASE，查找关于成人心脏手术期间使用抑肽酶导致肾功能障碍或死亡风险的非实验性研究。采用随机效应荟萃分析汇总各项研究的每个结局结果。采用分层分析和荟萃回归分析确定异质性来源。
共识别出11项相关研究并纳入分析，其中10项报告了肾功能障碍，7项报告了死亡情况。抑肽酶与肾功能障碍（风险比（RR）为1.42；95%置信区间为1.13 - 1.79）和长期死亡率（风险比（HR）为1.22；95%置信区间为1.08 - 1.39）相关。短期死亡率（RR为1.16；95%置信区间为0.84 - 1.58）和需要透析的肾衰竭（RR为1.17；95%置信区间为0.99 - 1.38）的汇总估计值较低。体外循环（CPB）时间可能处于因果路径上，是异质性的一个重要来源，CPB时间每增加10分钟，肾功能障碍风险增加29%（p = 0.03）。
尽管一些研究报告抑肽酶与心脏手术期间的肾脏结局无关联，但总体流行病学证据表明风险增加，且不能完全用输注红细胞（RBC）的需求来解释。流行病学研究还表明，与这些研究中使用的各种对照相比，抑肽酶与长期死亡率增加相关，尽管不能排除残余混杂因素。
