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

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

Beverly Winikof Lancet 2019; 394: 1011–21

Aim

To compare 3 oral anti-hypertensive in the treatment of hypertension in pregnancy. 

Rationale

Hypertensive disorders of pregnancy is a major problem. In resource limited settings the administration of intravenous agents can be a significant burden on those limited resources. If oral agents are equally efficacious, this would have a big impact. 

Design

Open label randomised controlled trial 

Setting

2 hospitals in Nagpur, India. One tertiary centre and its associated smaller hospital  

Population

894 Pregnant women 

Inclusion; Pregnant women (28 weeks plus) with bp >160/110 (measured twice)

Exclusion; Emergency surgery needed, emerging eclampsia, known fetal abnormality, significant comorbidity (asthma, coronary heart disease, type 1 diabetes) 

⅓ had no proteinuria, very few received magnesium or had deranged blood tests (<5% of each)

Intervention

Administration of either Nifedipine(10mg, escalated as needed), labetalol (100mg, escalated as needed) methodolpa (1000mg, no dose escalation). 

Magnesium prescribed as needed to both groups.

Control

Usual clinican care; these patients received less than 2 litres of fluid in the first 6 hours. Only 2 percent received vasopressors. 

Primary outcome

Blood pressure control within 6 hours (systolic bp 120-150 and diastolic 70-100) with no adverse effects. 

Results

84% of the nifedipine group achieved good control within 6 hours without adverse events. This was significantly more than the methyldopa group  (76%). There was no significant difference between the labetalol arm and the other treatment arms. 

Adverse outcomes are rare and similar between groups. 

Author's Discussion

These three medications are all good options for hypertensive pregnant patients with nifedipine seeming the most effective.

They also draw attention to the positive outcomes with frequent bp measurements and early administration of oral medications.  

Strengths

Randomised 

Large study

Expanded numbers to ensure sufficient power to detect difference.

Intention to treat analysis

Weakness

No direct comparison to intravenous therapy 

Largely outpatient non emergency study. 

Unblinded 

Unclear exactly what type of unit the patients were treated in, presumably a maternity unit; uncertain if applicable to an emergency generalist setting. 

 My humble opinion

Reassuring that methyldopa (the medication I am most used to ) and the simplest to administer is effective in reducing hypertension quickly in a stable pregnant hypertenisve patient. 

However, this is a very well cohort of patients with few complications that I would expect to respond well to oral medications, for a non-specialist it is difficult to know when to try and get away with oral therapy or to resort to IV. As an emergency physician, it would be nice to see this result repeated in a cohort who were slightly more unwell.