Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK.
Department of Obstetrics and Gynecology, Bordeaux University Hospital, Bordeaux, France.
Lancet. 2024 Oct 26;404(10463):1657-1667. doi: 10.1016/S0140-6736(24)02102-0.
Tranexamic acid is a recommended treatment for women with a clinical diagnosis of postpartum haemorrhage, but whether it can prevent bleeding is unclear. We conducted a systematic review and individual patient data (IPD) meta-analysis of randomised controlled trials to assess the effects of tranexamic acid in women giving birth.
In this systematic review and IPD meta-analysis, we searched the WHO International Clinical Trials Registry Platform from database inception to Aug 4, 2024 for randomised trials that assessed the effects of tranexamic acid in women giving birth. Trials were eligible if they were prospectively registered, placebo-controlled, included more than 500 women, and had a low risk of bias for random sequence generation and allocation concealment. IPD were requested from the trial investigators. The primary outcomes were the numbers of women with life-threatening bleeding and thromboembolic events. We used a one-stage model to analyse the data and explored whether the effect of tranexamic acid varied by the underlying risk of life-threatening bleeding, type of birth, presence of moderate or severe anaemia, or timing of administration (before or after a diagnosis of postpartum haemorrhage). This study is registered with PROSPERO, CRD42022345775.
We analysed data on 54 404 women from five trials. We obtained IPD for 43 409 women from four trials and aggregate data on 10 995 women from one trial. All trials had a low risk of bias. Life-threatening bleeding occurred in 178 (0·65%) of 27 300 women in the tranexamic acid group versus 230 (0·85%) of 27 093 women in the placebo group (pooled odds ratio [OR] 0·77 [95% CI 0·63-0·93]; p=0·008). There was no evidence that the effect of tranexamic acid varied by the underlying risk of life-threatening bleeding, type of birth, presence of moderate or severe anaemia or timing of administration. No significant difference was identified between tranexamic acid and placebo groups with regard to thromboembolic events: 50 (0·2%) of 26 571 women in the tranexamic acid group had fatal or non-fatal thromboembolic events versus 52 (0·2%) of 26 373 women in the placebo group (pooled OR 0·96 [0·65-1·41]; p=0·82) with no significant heterogeneity identified in the subgroup analyses.
Tranexamic acid reduces the risk of life-threatening postpartum bleeding. We found no evidence that tranexamic acid increases the risk of thrombosis. Although we do not recommend the use of tranexamic acid in all women giving birth, consideration should be given to its use before a diagnosis of postpartum haemorrhage in women at high risk of death.
The Bill & Melinda Gates Foundation.
氨甲环酸是一种被推荐用于治疗产后出血的药物，但它是否能预防出血仍不清楚。我们进行了一项系统评价和个体患者数据（IPD）荟萃分析，以评估氨甲环酸在分娩妇女中的疗效。
在这项系统评价和 IPD 荟萃分析中，我们从数据库建立到 2024 年 8 月 4 日，在世界卫生组织国际临床试验注册平台上搜索了评估氨甲环酸在分娩妇女中疗效的随机对照试验。试验如果是前瞻性注册、安慰剂对照、纳入超过 500 名妇女且随机序列生成和分配隐藏的偏倚风险低，则符合入选标准。我们向试验研究者请求了 IPD。主要结局是发生危及生命的出血和血栓栓塞事件的妇女人数。我们使用单阶段模型来分析数据，并探讨了氨甲环酸的效果是否因危及生命的出血的潜在风险、分娩类型、中度或重度贫血的存在以及给药时间（在产后出血诊断之前或之后）而有所不同。本研究在 PROSPERO 注册，CRD42022345775。
我们分析了来自五项试验的 54404 名妇女的数据。我们从四项试验中获得了 43409 名妇女的 IPD，并从一项试验中获得了 10995 名妇女的汇总数据。所有试验的偏倚风险都较低。在氨甲环酸组中，有 178 名（0.65%）27000 名妇女发生危及生命的出血，而在安慰剂组中，有 230 名（0.85%）27093 名妇女发生危及生命的出血（合并比值比 [OR] 0.77 [95%CI 0.63-0.93]；p=0.008）。没有证据表明氨甲环酸的效果因危及生命的出血的潜在风险、分娩类型、中度或重度贫血的存在或给药时间而异。在血栓栓塞事件方面，氨甲环酸组与安慰剂组之间没有显著差异：在氨甲环酸组中，有 50 名（0.2%）26571 名妇女发生致命或非致命性血栓栓塞事件，而在安慰剂组中，有 52 名（0.2%）26373 名妇女发生致命或非致命性血栓栓塞事件（合并 OR 0.96 [0.65-1.41]；p=0.82），亚组分析中未发现显著异质性。
氨甲环酸可降低产后出血危及生命的风险。我们没有发现氨甲环酸增加血栓形成风险的证据。尽管我们不建议在所有分娩妇女中使用氨甲环酸，但对于有死亡高风险的妇女，应考虑在产后出血诊断之前使用氨甲环酸。
比尔及梅琳达·盖茨基金会。
