Best Drug for Hypertensive Crisis in Pregnancy Is Judgment Call

Severe hypertension in pregnancy indicates treatment with an antihypertensive medication, but clinical experience and patient preference should guide the choice of which antihypertensive drug to use, suggested the results of an intervention review.¹

The goal of treatment of severe hypertension in pregnancy is to quickly lower blood pressure without causing sudden drops that may lead to dizziness, syncope, or fetal distress. However, it is unknown which antihypertensive drugs are most effective and safest during pregnancy. To gain insight, the Cochrane Pregnancy and Childbirth Group evaluated 35 randomized trials involving direct comparisons of antihypertensive agents in women with severe hypertension during pregnancy.

The available evidence was insufficient to recommend one antihypertensive agent over another. However, trends did emerge that support the avoidance of specific antihypertensives in pregnant women in hypertensive crisis.

Overall, calcium channel blockers (CCBs) better controlled persistent hypertension than hydralazine. Among women given CCBs, 8% had persistent high blood pressure, compared with 22% of women allocated to hydralazine. CCBs are not approved for use during pregnancy but are commonly used in this patient population despite a lack of safety data.

Independent of this review, there is some evidence that adverse fetomaternal events increase in conjunction with a CCB dose increase.² For the CCB nifedipine, doses of greater than 60 mg/d seem to be associated with the highest incidence of adverse events. However, nifedipine, among other antihypertensive agents, was not directly compared in the intervention review because of insufficient evidence.

Compared with the serotonin antagonist ketanserin, hydralazine more effectively controlled persistent hypertension. However, ketanserin was associated with fewer adverse effects and a lower risk of HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) than hydralazine.

The beta-blocker labetalol was associated with a lower risk of hypotension and a lower risk of cesarean section than diazoxide, which is typically reserved for hypertensive emergencies. However, the strength of the associations was borderline.

Persistent severe hypertension was poorly controlled with both nimodipine, a CCB, and magnesium sulfate, an anticonvulsant, although nimodipine performed slightly better than magnesium sulfate. In addition, nimodipine was associated with less risk of respiratory difficulties, fewer adverse effects, and less postpartum hemorrhage than magnesium sulfate.

The review authors made no recommendations for any particular antihypertensive but did suggest that nimodipine, diazoxide, and ketanserin should be avoided. Magnesium sulfate is indicated in patients who require an anticonvulsant for the prevention or treatment of eclampsia, but the drug should be avoided in all other cases of severe hypertension, advised the authors.

When managing very high blood pressure in pregnant women, physicians should choose the antihypertensive agent with which they have most experience and familiarity. The drug’s adverse-effect profile and maternal concerns about fetal drug exposure should also be considered.

Pertinent Points:
- A physician’s experience should guide drug choice when managing severe hypertension during pregnancy.
- Evidence indicates that nimodipine, diazoxide, and ketanserin should be avoided in pregnant women.
- Magnesium sulfate should be avoided in all cases of severe hypertension in pregnancy unless required for the prevention or treatment of seizures.

References:

1. Duley L, Meher S, Jones L. Drugs for treatment of very high blood pressure during pregnancy. Cochrane Database Syst Rev. 2013;7:CD001449. DOI: 10.1002/14651858.CD001449.pub3.
2. Khan K, Zamorea J, Lamont RE, et al. Safety concerns for the use of calcium channel blockers in pregnancy for the treatment of spontaneous preterm labour and hypertension: a systematic review and meta-regression analysis. J Matern Fetal Neonatal Med. 2010;23:1030-1038.