美国纽约Gynuity卫生项目Hillary Bracken研究组比较了口服降压药物（硝苯地平缓释片、拉贝洛尔和甲基多巴）治疗妊娠期重度高血压的效果。相关论文发表在2019年9月21日出版的《柳叶刀》杂志上。

在这项多中心、平行组、开放标签、随机对照试验中，研究组比较了印度那格浦尔两家公立医院孕妇口服抗高血压药的情况。参与者年龄均超过18岁，孕周大于28周，收缩压高于160 mmHg或舒张压高于110 mmHg，需要进行药物控制降压。

2015年4月1日至2017年8月21日，经过一系列的筛选，研究组共招募了894名符合条件的孕妇，将其随机分配，其中298名妇女口服硝苯地平10 mg，295名口服拉贝洛尔200 mg，301名口服甲基多巴1000 mg进行治疗。血压控制定义为6小时内收缩压为120-150 mmHg，舒张压为70-100 mmHg，且无不良后果。

硝苯地平组有84%的患者血压得到控制，显著高于甲基多巴组（76%）。然而硝苯地平组或甲基多巴组与拉贝洛尔组的血压控制率（77%）相比均无统计学差异。共发生7例严重不良事件，其中拉贝洛尔组有1例孕妇发生产时癫痫，2例死产；硝苯地平组有1例死产；甲基多巴组有3例死产。

总之，所有抗高血压药都能使大多数女性的血压降低到参考范围。作为单一药物，硝苯地平缓释片的降压效果优于拉贝洛尔或甲基多巴。这三种口服药物均可作为资源不足地区治疗妊娠期重度高血压的初始选择。

据悉，每十个孕妇中就有一名患妊娠期高血压，血压严重升高的孕妇需进行治疗，以降低产妇并发症的风险。紧急治疗方案通常包括静脉注射药物，需要打开静脉通路并谨慎地进行胎儿监护，这在一些繁忙或资源不足的环境中可能无法实现。

附：英文原文

Title: Oral antihypertensive regimens (nifedipine retard, labetalol, and methyldopa) for management of severe hypertension in pregnancy: an open-label, randomised controlled trial

Author: Thomas Easterling, Shuchita Mundle, Hillary Bracken, Seema Parvekar, Sulabha Mool, Laura A Magee, Peter von Dadelszen, Tara Shochet, Beverly Winikoff

Issue&Volume: Volume 394 Number 10203

Summary: 

Background

Hypertension is the most common medical disorder in pregnancy, complicating one in ten pregnancies. Treatment of severely increased blood pressure is widely recommended to reduce the risk for maternal complications. Regimens for the acute treatment of severe hypertension typically include intravenous medications. Although effective, these drugs require venous access and careful fetal monitoring and might not be feasible in busy or low-resource environments. We therefore aimed to compare the efficacy and safety of three oral drugs, labetalol, nifedipine retard, and methyldopa for the management of severe hypertension in pregnancy.

Methods

In this multicentre, parallel-group, open-label, randomised controlled trial, we compared these oral antihypertensives in two public hospitals in Nagpur, India. Pregnant women were eligible for the trial if they were aged at least 18 years; they were pregnant with fetuses that had reached a gestational age of at least 28 weeks; they required pharmacological blood pressure control for severe hypertension (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥110 mm Hg); and were able to swallow oral medications. Women were randomly assigned to receive 10 mg oral nifedipine, 200 mg oral labetalol (hourly, in both of which the dose could be escalated if hypertension was maintained), or 1000 mg methyldopa (a single dose, without dose escalation). Masking of participants, study investigators, and care providers to group allocation was not possible because of different escalation protocols in the study groups. The primary outcome was blood pressure control (defined as 120–150 mm Hg systolic blood pressure and 70–100 mm Hg diastolic blood pressure) within 6 h with no adverse outcomes. This study is registered with ClinicalTrials.gov, number NCT01912677, and the Clinical Trial Registry, India, number ctri/2013/08/003866.

Findings

Between April 1, 2015, and Aug 21, 2017, we screened 2307 women for their inclusion in the study. We excluded 1413 (61%) women who were ineligible, declined to participate, had impending eclampsia, were in active labour, or had a combination of these factors. 11 (4%) women in the nifedipine group, ten (3%) women in the labetalol group, and 11 (4%) women in the methyldopa group were ineligible for treatment (because they had only one qualifying blood pressure measurement) or had treatment stopped (because of delivery or transfer elsewhere). 894 (39%) women were randomly assigned to a treatment group and were included in the intention-to-treat analysis: 298 (33%) women were assigned to receive nifedipine, 295 (33%) women were assigned to receive labetalol, and 301 (33%) women were assigned to receive methyldopa. The primary outcome was significantly more common in women in the nifedipine group than in those in the methyldopa group (249 [84%] women vs 230 [76%] women; p=0·03). However, the primary outcome did not differ between the nifedipine and labetalol groups (249 [84%] women vs 228 [77%] women; p=0·05) or the labetalol and methyldopa groups (p=0·80). Seven serious adverse events (1% of births) were reported during the study: one (<1%) woman in the labetalol group had an intrapartum seizure and six (1%) neonates (one [<1%] neonate in the nifedipine group, two [1%] neonates in the labetalol group, and three [1%] neonates in the methyldopa group) were stillborn. No birth had more than one adverse event.

Interpretation

All oral antihypertensives reduced blood pressure to the reference range in most women. As single drugs, nifedipine retard use resulted in a greater frequency of primary outcome attainment than labetalol or methyldopa use. All three oral drugs—methyldopa, nifedipine, and labetalol—are viable initial options for treating severe hypertension in low-resource settings.

Funding

PREEMPT (University of British Columbia, Vancouver, BC, Canada; grantee of Bill & Melinda Gates Foundation).

DOI: 10.1016/S0140-6736(19)31282-6

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31282-6/fulltext