Control of Hypertension In Pregnancy Study randomised controlled trial-are the results dependent on the choice of labetalol or methyldopa?

L A Magee; CHIPS Study Group; P von Dadelszen; J Singer; T Lee; E Rey; S Ross; E Asztalos; K E Murphy; J Menzies; J Sanchez; A Gafni; A Gruslin; M Helewa; E Hutton; G Koren; S K Lee; A G Logan; J W Ganzevoort; R Welch; J G Thornton; J-M Moutquin

doi:10.1111/1471-0528.13568

Control of Hypertension In Pregnancy Study randomised controlled trial-are the results dependent on the choice of labetalol or methyldopa?

BJOG. 2016 Jun;123(7):1135-41. doi: 10.1111/1471-0528.13568. Epub 2015 Aug 11.

Authors

L A Magee^{1

2

3}; CHIPS Study Group; P von Dadelszen^{2

3}, J Singer^{3

4}, T Lee⁴, E Rey⁵, S Ross⁶, E Asztalos^{7

8

9}, K E Murphy^{8

9}, J Menzies², J Sanchez⁹, A Gafni¹⁰, A Gruslin¹¹, M Helewa¹², E Hutton¹³, G Koren⁷, S K Lee⁷, A G Logan¹⁴, J W Ganzevoort¹⁵, R Welch¹⁶, J G Thornton¹⁷, J-M Moutquin¹⁸

Affiliations

¹ Medicine, University of British Columbia, Vancouver, BC, Canada.
² Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC, Canada.
³ School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
⁴ Centre for Health Evaluation and Outcome Sciences (CHÉOS), Providence Health Care Research Institute, UBC, Vancouver, BC, Canada.
⁵ Medicine and Obstetrics and Gynaecology, University of Montreal, Montreal, QC, Canada.
⁶ Obstetrics and Gynaecology, University of Alberta, Edmonton, AB, Canada.
⁷ Paediatrics, University of Toronto, Toronto, ON, Canada.
⁸ Obstetrics and Gynaecology, University of Toronto, Toronto, ON, Canada.
⁹ The Centre for Mother, Infant and Child Research, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
¹⁰ Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
¹¹ Obstetrics and Gynaecology, University of Ottawa, Ottawa, ON, Canada.
¹² Obstetrics and Gynaecology, University of Manitoba, Winnipeg, MB, Canada.
¹³ Obstetrics and Gynaecology, McMaster University, Hamilton, ON, Canada.
¹⁴ Medicine, University of Toronto, Toronto, ON, Canada.
¹⁵ Obstetrics and Gynaecology, University of Amsterdam, Amsterdam, the Netherlands.
¹⁶ Obstetrics and Gynaecology, Derriford Hospital, Plymouth, UK.
¹⁷ Obstetrics and Gynaecology, University of Nottingham, Nottingham, UK.
¹⁸ Obstetrics and Gynaecology, Universite de Sherbrooke, Sherbrooke, QC, Canada.

PMID: 26259808
DOI: 10.1111/1471-0528.13568

Abstract

Objective: To determine whether the difference in outcomes between 'less tight' (target diastolic blood pressure [dBP] of 100 mmHg) versus 'tight' control (target dBP of 85 mmHg) in the CHIPS Trial (ISRCTN 71416914, http://pre-empt.cfri.ca/;CHIPS) depended on the choice of labetalol or methyldopa, the two most commonly used antihypertensive agents in CHIPS.

Design: Secondary analysis of CHIPS Trial data.

Setting: International multicentre randomised controlled trial (94 sites, 15 countries).

Population or sample: A total of 987 women with non-severe non-proteinuric pregnancy hypertension.

Methods: Logistic regression was used for comparisons of 'less tight' versus 'tight' control among women treated with labetalol (but not methydopa) versus methyldopa (but not labetalol). Analyses were adjusted for the influence of baseline factors, including use of any antihypertensive therapy at randomisation.

Main outcome measures: Main CHIPS Trial outcomes: primary (perinatal loss or high-level neonatal care for > 48 hours), secondary (serious maternal complications), birthweight < 10th centile, severe maternal hypertension, pre-eclampsia, and delivery at < 34 or < 37 weeks.

Results: Of 987 women in CHIPS, antihypertensive therapy was taken by 566 women at randomisation (labetalol 111 ['less tight'] versus 127 ['tight'] or methyldopa 126 ['less tight'] versus 117 ['tight']) and 815 women after randomisation (labetalol 186 ['less tight'] versus 247 ['tight'] and methyldopa by 98 ['less tight'] versus 126 ['tight']). Following adjustment, odds ratios for outcomes in 'less tight' versus 'tight' control were similar between antihypertensive groups according to 'at randomisation' and 'after randomisation' therapy.

Conclusion: Outcomes for 'less tight' versus 'tight' control were not dependent on use of methyldopa or labetalol.

Tweetable abstract: In the CHIPS Trial, maternal and infant outcomes were not dependent on use of labetalol or methyldopa.

Keywords: Antihypertensive therapy; hypertension; labetalol; methyldopa; pregnancy.

Publication types

Comparative Study
Multicenter Study
Randomized Controlled Trial

MeSH terms

Adult
Antihypertensive Agents / therapeutic use*
Blood Pressure / drug effects*
Clinical Decision-Making
Female
Humans
Hypertension / drug therapy
Hypertension / physiopathology
Hypertension, Pregnancy-Induced / drug therapy*
Hypertension, Pregnancy-Induced / physiopathology
Infant, Low Birth Weight
Labetalol / therapeutic use*
Methyldopa / therapeutic use*
Pre-Eclampsia / etiology
Pre-Eclampsia / physiopathology
Pregnancy
Pregnancy Complications, Cardiovascular / drug therapy
Pregnancy Complications, Cardiovascular / physiopathology
Premature Birth / etiology
Prenatal Care / methods
Risk Factors
Treatment Outcome

Substances

Antihypertensive Agents
Methyldopa
Labetalol