​​普伐他汀治疗早发型子痫前期：一项随机、盲法、安慰剂对照试验

【目的】

子痫前期患者循环内可溶性fms样酪氨酸激酶（sFlt-1）水平上升。他汀类药物能够降低培养细胞中sFlt-1水平，改善子痫前期动物模型中妊娠结局。我们研究普伐他汀对于子痫前期患者血清sFt-1的影响。

【设计】

双盲（受试者和研究者），原理论证，安慰剂对照试验。

【处所】

英国15家产科机构

【人群】

我们采用最小算法纳入62名早发型子痫前期患者（孕24+0周至31+6周）自随机分组至分娩，每日服用普伐他汀40mg（n=30）或配对安慰剂组（n=32）。

【主要测量结局】

随机分组后3天内血清sFlt-1平均水平差异。

【结果】

随机分组后3天内普伐他汀组（n=27）和安慰剂组（n=29）母体血清sFlt-1水平平均差值为292pg/ml（95CI -1175-592；p=0.5），1-14天内差值为48pg/ml（95CI -1009-913；p=0.9）。随机分组后，普伐他汀组患者孕周时长与安慰剂组相似（风险比 0.84; 95% CI 0.50–1.40; P = 0.6）。随机分组至分娩平均时间，在普伐他汀组为9天（四分位数5-14天），安慰剂组7天（四分位数4-11天）。安慰剂组有3例围产儿死亡，普伐他汀组无围产儿死亡或药物引发的不良事件。

【结论】

我们未发现普伐他汀降低早发型子痫前期母体血清sFlt-1水平的证据。普伐他汀未发现对围产儿存在不良效应。

试验流程

两组孕妇血清sFlt-1、PIGF、sFlt-1/PIGF水平比较

Pravastatin for early‐onset pre‐eclampsia: a randomised, blinded,placebo‐controlled trial

AAhmed，DJWilliams，VCheed LJMiddleton ，SAhmad ，KWang， ATVince， PHewett， KSpencer， KSKhan ，JPDaniels for theStAmP trial Collaborative Group

First published:12 November 2019

 https://doi.org/10.1111/1471-0528.16013

Trial Registration: InternationalClinical Trial Registry Number 23410175. www.isrctn.com/ISRCTN23410175

【Objective】

Women with pre‐eclampsia have elevatedcirculating levels of soluble fms‐like tyrosine kinase‐1 (sFlt‐1). Statins canreduce sFlt‐1 from cultured cells and improve pregnancy outcome in animals witha pre‐eclampsia‐like syndrome. We investigated the effect of pravastatin onplasma sFlt‐1 levels during pre‐eclampsia.

【Design】

Blinded (clinician and participant), proofof principle, placebo‐controlled trial.

【Setting】

Fifteen UK maternity units.

【Population】

We used a minimisation algorithm to assign62 women with early‐onset pre‐eclampsia (24+0–31+6 weeks of gestation) toreceive pravastatin 40 mg daily (n = 30) or matched placebo (n = 32),from randomisation to childbirth.

【Primary outcome】

Difference in mean plasma sFlt‐1 levelsover the first 3 days following randomisation.

【Results】

The difference in the mean maternal plasmasFlt‐1 levels over the first 3 days after randomisation between thepravastatin (n = 27) and placebo (n = 29) groups was292 pg/ml (95% CI −1175 to 592; P = 0.5), and over days1–14 was 48 pg/ml (95% CI −1009 to 913; P = 0.9). Women whoreceived pravastatin had a similar length of pregnancy following randomisationcompared with those who received placebo (hazard ratio 0.84; 95% CI0.50–1.40; P = 0.6). The median time from randomisation tochildbirth was 9 days (interquartile range [IQR] 5–14 days) for thepravastatin group and 7 days (IQR 4–11 days) for the placebo group.There were three perinatal deaths in the placebo‐treated group and no deaths orserious adverse events attributable to pravastatin.

【Conclusions】

We found no evidence that pravastatinlowered maternal plasma sFlt‐1 levels once early‐onset pre‐eclampsia haddeveloped. Pravastatin appears to have no adverse perinatal effects.

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  （编译 王伟琳）​​​​​