重组活化因子 VII 在随机临床试验中的安全性。
Safety of recombinant activated factor VII in randomized clinical trials.
机构信息
Department of Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
出版信息
N Engl J Med. 2010 Nov 4;363(19):1791-800. doi: 10.1056/NEJMoa1006221.
BACKGROUND
The use of recombinant activated factor VII (rFVIIa) on an off-label basis to treat life-threatening bleeding has been associated with a perceived increased risk of thromboembolic complications. However, data from placebo-controlled trials are needed to properly assess the thromboembolic risk. To address this issue, we evaluated the rate of thromboembolic events in all published randomized, placebo-controlled trials of rFVIIa used on an off-label basis.
METHODS
We analyzed data from 35 randomized clinical trials (26 studies involving patients and 9 studies involving healthy volunteers) to determine the frequency of thromboembolic events. The data were pooled with the use of random-effects models to calculate the odds ratios and 95% confidence intervals.
RESULTS
Among 4468 subjects (4119 patients and 349 healthy volunteers), 401 [corrected] had thromboembolic events (9.0%). [corrected] Rates of arterial thromboembolic events among all 4468 subjects were higher among those who received rFVIIa than among those who received placebo (5.5% vs. 3.2%, P=0.003). Rates of venous thromboembolic events were similar among subjects who received rFVIIa and those who received placebo (5.3% vs. 5.7%). Among subjects who received rFVIIa, 2.9% had coronary arterial thromboembolic events, as compared with 1.1% of those who received placebo (P=0.002). Rates of arterial thromboembolic events were higher among subjects who received rFVIIa than among subjects who received placebo, particularly among those who were 65 years of age or older (9.0% vs. 3.8%, P=0.003); the rates were especially high among subjects 75 years of age or older (10.8% vs. 4.1%, P=0.02).
CONCLUSIONS
In a large and comprehensive cohort of persons in placebo-controlled trials of rFVIIa, treatment with high doses of rFVIIa on an off-label basis significantly increased the risk of arterial but not venous thromboembolic events, especially among the elderly. (Funded by Novo Nordisk.).
背景
在超适应证情况下使用重组活化因子 VII（rFVIIa）治疗危及生命的出血与血栓栓塞并发症风险增加有关。然而，需要安慰剂对照试验的数据来正确评估血栓栓塞风险。为了解决这个问题，我们评估了所有已发表的 rFVIIa 超适应证使用的安慰剂对照随机临床试验中血栓栓塞事件的发生率。
方法
我们分析了来自 35 项随机临床试验（26 项涉及患者的研究和 9 项涉及健康志愿者的研究）的数据，以确定血栓栓塞事件的频率。使用随机效应模型对数据进行汇总，以计算比值比和 95%置信区间。
结果
在 4468 名受试者（4119 名患者和 349 名健康志愿者）中，有 401 名发生血栓栓塞事件（9.0%）。[校正后]所有 4468 名受试者中，接受 rFVIIa 治疗的受试者动脉血栓栓塞事件发生率高于接受安慰剂治疗的受试者（5.5% vs. 3.2%，P=0.003）。接受 rFVIIa 治疗和接受安慰剂治疗的受试者静脉血栓栓塞事件发生率相似（5.3% vs. 5.7%）。接受 rFVIIa 治疗的受试者中，有 2.9%发生冠状动脉血栓栓塞事件，而接受安慰剂治疗的受试者中为 1.1%（P=0.002）。接受 rFVIIa 治疗的受试者动脉血栓栓塞事件发生率高于接受安慰剂治疗的受试者，尤其是 65 岁及以上的受试者（9.0% vs. 3.8%，P=0.003）；75 岁及以上的受试者中发生率特别高（10.8% vs. 4.1%，P=0.02）。
结论
在 rFVIIa 的安慰剂对照试验中，大量且全面的受试者队列中，超适应证使用大剂量 rFVIIa 显著增加了动脉血栓栓塞事件的风险，但不增加静脉血栓栓塞事件的风险，尤其是在老年人中。（由 Novo Nordisk 资助）。
Zotero 插件