Labetalol Versus Nifedipine as Antihypertensive Treatment for Chronic Hypertension in Pregnancy

Data to inform prescribing of antihypertensive treatments for chronic hypertension in pregnancy are sparse and subsequently no consensus on the optimal agent(s) exists. The prevalence of chronic hypertension in pregnancy is estimated at 3%, but this figure is set to increase with rising maternal age and the global obesity epidemic. Given that chronic hypertension is associated with significantly increased adverse maternal and perinatal outcomes compared with the general pregnant population, defining optimal antihypertensive treatment(s) is warranted. A Cochrane review examining trials (including >4000 women) in mild to moderate hypertension in pregnancy (combining chronic and gestational hypertension) concluded that although the incidence of severe hypertension is reduced with antihypertensive treatment, no reduction in the incidence of adverse maternal and perinatal outcomes has been demonstrated. There have been additional concerns that antihypertensive treatment might increase the risk of fetal growth restriction. However, more recent evidence from the Control of Hypertension In Pregnancy Study concluded that tight control to a diastolic target of 85 mm Hg (compared with less-tight control to a diastolic target of 105 mm Hg) did not increase the risk of pregnancy loss or high-level neonatal care in women with nonsevere chronic and gestational hypertension, no proteinuria, and a singleton pregnancy. This study also demonstrated that the incidence of severe maternal hypertension was significantly increased with less-tight control, which was associated with an increased risk of serious Abstract—Data from randomized controlled trials to guide antihypertensive agent choice for chronic hypertension in pregnancy are limited; this study aimed to compare labetalol and nifedipine, additionally assessing the impact of ethnicity on treatment efficacy. Pregnant women with chronic hypertension (12–27 weeks’ gestation) were enrolled at 4 UK centers (August 2014 to October 2015). Open-label first-line antihypertensive treatment was randomly assigned: labetalol(200–1800 mg/d) or nifedipine-modified release (20–80 mg/d). Analysis included 112 women (98%) who completed the study (labetalol n=55, nifedipine n=57). Maximum blood pressure after randomization was 161/101 mm Hg with labetalol versus 163/105 mm Hg with nifedipine (mean difference systolic: 1.2 mm Hg [−4.9 to 7.2 mm Hg], diastolic: 3.3 mm Hg [−0.6 to 7.3 mm Hg]). Mean blood pressure was 134/84 mm Hg with labetalol and 134/85 mm Hg with nifedipine (mean difference systolic: 0.3 mm Hg [−2.8 to 3.4 mm Hg], and diastolic: −1.9 mm Hg [−4.1 to 0.3 mm Hg]). Nifedipine use was associated with a 7.4-mm Hg reduction (−14.4 to −0.4 mm Hg) in central aortic pressure, measured by pulse wave analysis. No difference in treatment effect was observed in black women (n=63), but a mean 4 mm Hg reduction (−6.6 to −0.8 mm Hg; P=0.015) in brachial diastolic blood pressure was observed with labetalol compared with nifedipine in non-black women (n=49). Labetalol and nifedipine control mean blood pressure to target in pregnant women with chronic hypertension. This study provides support for a larger definitive trial scrutinizing the benefits and side effects of first-line antihypertensive treatment. Clinical Trial Registration—URL: https://www.isrctn.com. Unique identifier: ISRCTN40973936. (Hypertension. 2017;70:00-00. DOI: 10.1161/HYPERTENSIONAHA.117.09972.) • Online Data Supplement