Elsevier

Pregnancy Hypertension

Volume 18, October 2019, Pages 179-187
Pregnancy Hypertension

Review article
First-line antihypertensive treatment for severe hypertension in pregnancy: A systematic review and network meta-analysis

https://doi.org/10.1016/j.preghy.2019.09.019Get rights and content

Highlights

  • Comprehensive summary of the evidence on managing severe hypertension in pregnancy.

  • There is good evidence for management of severe hypertension using oral nifedipine.

  • Superiority of nifedipine to hydralazine should be further investigated.

Abstract

Background

Hydralazine, labetalol, and nifedipine are the recommended first-line treatments for severe hypertension in pregnancy. While all three are effective, there is a lack of sufficient evidence regarding their comparative safety and efficacy.

Objective

To determine the comparative safety and efficacy of the first-line treatment options for severe hypertension in pregnancy.

Methods

A systematic search of Medline, Embase, and Cochrane Central Register of Controlled Trials up to May 31, 2018 was conducted. RCTs in pregnancy comparing a first-line antihypertensive agent to another first-line agent for the treatment of severe hypertension in pregnancy. Screening, data abstraction, and quality assessment were done by two independent reviewers. To estimate relative effects from all available evidence, a Bayesian network meta-analysis with vague priors was conducted.

Main Results

Of the 1330 publications identified, 17 RCTs comprised of a total of 1591 women met our selection criteria. For successful treatment of severe hypertension, nifedipine was found to be superior to hydralazine (OR 4.13 [95% CrI 1.01–20.75]) but not labetalol (OR 3.43 [95% CrI 0.94–19.95]). This was not associated with an increased risk for caesarean delivery or maternal side effects. There was no significant difference between labetalol and hydralazine.

Conclusions

Given the results of this systematic review and network meta-analysis, maternity care providers should feel comfortable initiating management of severe hypertension in pregnancy using oral nifedipine.

Introduction

It is estimated that hypertensive disorders of pregnancy (HDP) complicate 5–10% of pregnancies worldwide and account for 18% of maternal deaths [1], [2]. HDPs are responsible for 25% of maternal deaths in Latin America and the Caribbean, 16% in developed countries, and 9% in Asia and Africa [3]. As the leading contributor to maternal and neonatal mortality and morbidity across the world [1], optimal treatment of HDPs represents an important avenue for scientific inquiry.

Severe hypertension in pregnancy is defined as systolic blood pressure (sBP) ≥160 mmHg and/or diastolic blood pressure (dBP) ≥110 mmHg [4]. Severe hypertension in pregnancy is associated with a number of serious adverse events for mother and child. It increases the risk of maternal morbidities, including: stroke, maternal-end organ damage, abnormal clotting, postpartum hemorrhage, and placental abruption. In addition, the fetus is at increased risk of intrauterine growth restriction, premature delivery, and low Apgar score [1], [5], [6], [7]. Another serious concern is the development of severe hypertension into preeclampsia, the most dangerous of HDPs [8].

For severe hypertension in pregnancy, there is general consensus supporting immediate intervention with antihypertensive agents [4], [8]. Current clinical practice guidelines (CPGs) recommend intravenous (IV) hydralazine, IV labetalol, and oral nifedipine as the first-line antihypertensive treatments [5], [6], [9], [10], [11]. While all three are effective antihypertensive medications, there is a lack of sufficient evidence regarding their comparative safety and efficacy [8], [12], [13].

Based on the current body of evidence, the decision of which first-line antihypertensive treatment to use is based on physician experience, convenience of use, local availability, and cost [8], [12], [13], [14]. Since effective management of severe hypertension is vital for safe progression of pregnancy, a more evidence-based approach is necessary. Network meta-analyses (NMA) use direct and indirect evidence to strengthen treatment comparisons and allow for effect estimates between interventions that have not been compared head-to-head and for the estimation of the relative efficacy and safety of the interventions under investigation [15].

Therefore, we conducted a systematic review and NMA to determine the comparative effectiveness and safety of hydralazine, labetalol, and nifedipine for severe hypertension in pregnancy.

Section snippets

Systematic search

We conducted a comprehensive systematic search of Medline (ovid), Embase (ovid), and Cochrane central register of controlled trials (CCRT) up to October 20, 2015, then updated until May 31, 2018. The search strategies used are outlined in Appendix S1. The Medline search strategy was verified by comparing the results with 10 RCTs known to be relevant and peer reviewed by an information specialist using PRESS [16].

Study selection, data extraction, and study quality assessment

Screening, data abstraction, and assessment of the quality of each study was done

Data synthesis

To estimate relative effects from all available evidence (direct and indirect), a Bayesian network meta-analysis with vague (non-informative) priors and a homogenous variance structure was conducted for outcomes with sufficient evidence. Relative effects were calculated as odds ratios (ORs) with 95% credible intervals (CrI) using both a fixed and random effects model. The analysis was done using 5000 burn-ins and 40,000 iterations with NetMetaXL – a Bayesian network meta-analysis tool that uses

Study characteristics

Of the 1330 publications identified, 17 RCTs comprising a total of 1591 women met the selection criteria (Fig. 1) [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37].

Overall, there were 595 patients (37.4%) receiving labetalol, 598 (37.6%) receiving hydralazine, and 398 (25%) receiving nifedipine. All labetalol and hydralazine arms had an intravenous (IV) route of administration. Of the 11 trials with a nifedipine arm, nine orally administered

Main findings

We have performed a network meta-analysis to assess the safety and efficacy of three widely used antihypertensive treatments in the context of severe hypertension in pregnancy. Through the use of both direct and indirect evidence, this systematic review suggests that oral nifedipine improves successful treatment of hypertension with no observed increase in risk for caesarean delivery or maternal side effects relative to IV hydralazine and with no significant difference to IV labetalol.

A recent

Conclusion

Given the results of this systematic review and the network meta-analysis, maternity care providers should feel comfortable initiating management of severe hypertension in pregnancy using oral nifedipine. Further efforts are needed on the direct comparison between nifedipine and hydralazine as well as educational and translational studies, and evaluation of the implementation of nifedipine as first-line treatment for severe hypertension in pregnancy.

Acknowledgements

Not applicable.

Disclosure of interests

The authors declare no conflict of interest.

Contribution of authors

Sepand Alavifard contributed to the study conception, planning, performing the systemic review, network meta-analysis, and manuscript preparation.

Dr. Rebecca Chase contributed to performing the systematic review and preparation of this manuscript.

Andréanne Chaumont contributed to performing the systematic review and preparation of this manuscript.

Dr. Ghayath Janoudi contributed to the study conception, planning, data analysis, and manuscript preparation.

Dr. Andrea Lanes contributed to the study

Funding

This project was funded in part by the University of Ottawa Scholarship in Maternal and Neonatal Medicine.

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      As such, in Committee Opinion #767 the American College of Obstetricians and Gynecologists (ACOG) recommends that treatment be initiated as soon as possible with a goal of 30–60 min after confirming the severe range blood pressure [8]. Appropriate first-line medications are intravenous (IV) labetalol, IV hydralazine, or immediate release oral nifedipine [9–11]. Additionally, given that standardized guidelines have been shown to improve clinical outcomes in obstetrics and beyond [12–14], ACOG also recommends implementation of standardized order sets to expedite treatment and reduce adverse outcomes.

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