Meyer Guy, Planquette Benjamin, Sanchez Olivier
Service de Pneumologie-soins intensifs, Hôpital Européen Georges Pompidou, Assistance Publique Hopitaux de Paris, 20 rue Leblanc, 75015, Paris, France.
Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Curr Atheroscler Rep. 2015 Dec;17(12):68. doi: 10.1007/s11883-015-0546-1.
Controversy over the role of fibrinolysis in patients with intermediate-risk pulmonary embolism (PE) has persisted because of the lack of adequately sized trials. The PEITHO study now allows a more precise estimate of the risk to benefit ratio of fibrinolysis in these patients. This trial enrolled patients with intermediate-risk PE who were randomized to receive heparin with either tenecteplase or placebo. Fibrinolysis was associated with a significant reduction in the combined end-point of death or hemodynamic decompensation, but also with a significant increase in the risk of major bleeding. The primary efficacy end-point occurred in 2.6 % of the patients in the tenecteplase group and in 5.6 % of the patients in the placebo group (OR, 0.44; 95 % CI, 0.23 to 0.87), conversely, major extracranial bleeding occurred in 6.3 % and 1.2 % in the tenecteplase and placebo groups, respectively (OR, 5.55; 95 % CI, 2.3 to 13.39) and stroke occurred in 2.4 % and in 0.2 % of the patients in the tenecteplase group and in the placebo group, respectively (OR, 12.10; 95 % CI, 1.57 to 93.39). No difference was observed for the risk of death alone and the risk of full-dose thrombolytic therapy outweighs its benefit in patients with intermediate-risk PE. Recent meta-analyses suggest that fibrinolysis may be associated with a slight reduction in overall mortality offset by an increase in major bleeding. Two pilot studies suggest that a reduced dose of fibrinolysis may produce significant hemodynamic improvement with a low risk of major bleeding. These options need to be evaluated in larger studies including patients with a higher risk of adverse outcome than those included in the PEITHO study.
由于缺乏足够规模的试验，关于纤维蛋白溶解在中度风险肺栓塞（PE）患者中的作用一直存在争议。PEITHO研究现在能够更精确地估计这些患者中纤维蛋白溶解的风险效益比。该试验纳入了中度风险PE患者，将其随机分为接受肝素联合替奈普酶或安慰剂治疗。纤维蛋白溶解与死亡或血流动力学失代偿这一联合终点的显著降低相关，但也与大出血风险的显著增加相关。替奈普酶组2.6%的患者和安慰剂组5.6%的患者出现主要疗效终点（OR，0.44；95%CI，0.23至0.87），相反，替奈普酶组和安慰剂组分别有6.3%和1.2%的患者发生重大颅外出血（OR，5.55；95%CI，2.3至13.39），替奈普酶组和安慰剂组分别有2.4%和0.2%的患者发生卒中（OR，12.10；95%CI，1.57至93.39）。单独死亡风险未观察到差异，对于中度风险PE患者，全剂量溶栓治疗的风险超过其益处。近期的荟萃分析表明，纤维蛋白溶解可能与总体死亡率略有降低相关，但被大出血增加所抵消。两项试点研究表明，降低剂量的纤维蛋白溶解可能会显著改善血流动力学，且大出血风险较低。这些选择需要在更大规模研究中进行评估，研究对象为不良结局风险高于PEITHO研究中纳入患者的人群。
