Mayer Stephan A, Brun Nikolai C, Begtrup Kamilla, Broderick Joseph, Davis Stephen, Diringer Michael N, Skolnick Brett E, Steiner Thorsten
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, USA.
N Engl J Med. 2005 Feb 24;352(8):777-85. doi: 10.1056/NEJMoa042991.
Intracerebral hemorrhage is the least treatable form of stroke and is associated with high mortality. Among patients who undergo computed tomography (CT) within three hours after the onset of intracerebral hemorrhage, one third have an increase in the volume of the hematoma related to subsequent bleeding. We sought to determine whether recombinant activated factor VII (rFVIIa) can reduce hematoma growth after intracerebral hemorrhage.
We randomly assigned 399 patients with intracerebral hemorrhage diagnosed by CT within three hours after onset to receive placebo (96 patients) or 40 microg of rFVIIa per kilogram of body weight (108 patients), 80 microg per kilogram (92 patients), or 160 microg per kilogram (103 patients) within one hour after the baseline scan. The primary outcome measure was the percent change in the volume of the intracerebral hemorrhage at 24 hours. Clinical outcomes were assessed at 90 days.
Hematoma volume increased more in the placebo group than in the rFVIIa groups. The mean increase was 29 percent in the placebo group, as compared with 16 percent, 14 percent, and 11 percent in the groups given 40 microg, 80 microg, and 160 microg of rFVIIa per kilogram, respectively (P=0.01 for the comparison of the three rFVIIa groups with the placebo group). Growth in the volume of intracerebral hemorrhage was reduced by 3.3 ml, 4.5 ml, and 5.8 ml in the three treatment groups, as compared with that in the placebo group (P=0.01). Sixty-nine percent of placebo-treated patients died or were severely disabled (as defined by a modified Rankin Scale score of 4 to 6), as compared with 55 percent, 49 percent, and 54 percent of the patients who were given 40, 80, and 160 microg of rFVIIa, respectively (P=0.004 for the comparison of the three rFVIIa groups with the placebo group). Mortality at 90 days was 29 percent for patients who received placebo, as compared with 18 percent in the three rFVIIa groups combined (P=0.02). Serious thromboembolic adverse events, mainly myocardial or cerebral infarction, occurred in 7 percent of rFVIIa-treated patients, as compared with 2 percent of those given placebo (P=0.12).
Treatment with rFVIIa within four hours after the onset of intracerebral hemorrhage limits the growth of the hematoma, reduces mortality, and improves functional outcomes at 90 days, despite a small increase in the frequency of thromboembolic adverse events.
脑出血是最难治疗的中风类型，且死亡率很高。在脑出血发病后三小时内接受计算机断层扫描（CT）的患者中，三分之一患者的血肿体积会因随后的出血而增大。我们试图确定重组活化因子VII（rFVIIa）能否减少脑出血后的血肿生长。
我们将399例脑出血发病后三小时内经CT确诊的患者随机分组，在基线扫描后一小时内，分别给予安慰剂（96例患者）或每千克体重40微克rFVIIa（108例患者）、每千克体重80微克（92例患者）或每千克体重160微克（103例患者）。主要结局指标是24小时时脑出血体积的百分比变化。在90天时评估临床结局。
安慰剂组的血肿体积增加幅度大于rFVIIa组。安慰剂组平均增加29%，而每千克体重给予40微克、80微克和160微克rFVIIa的组分别增加16%、14%和11%（三个rFVIIa组与安慰剂组比较，P = 0.01）。与安慰剂组相比，三个治疗组的脑出血体积增长分别减少3.3毫升、4.5毫升和5.8毫升（P = 0.01）。接受安慰剂治疗的患者中有69%死亡或严重残疾（根据改良Rankin量表评分为4至6分定义），而接受每千克体重40微克、80微克和160微克rFVIIa治疗的患者分别为55%、49%和54%（三个rFVIIa组与安慰剂组比较，P = 0.004）。接受安慰剂治疗的患者90天死亡率为29%，而三个rFVIIa组合并为18%（P = 0.02）。接受rFVIIa治疗的患者中有7%发生严重血栓栓塞不良事件，主要是心肌梗死或脑梗死，而接受安慰剂治疗的患者为2%（P = 0.12）。
脑出血发病后四小时内使用rFVIIa治疗可限制血肿生长，降低死亡率，并改善90天时的功能结局，尽管血栓栓塞不良事件的发生率略有增加。
