Oral Antihypertensives for Management of Severe Hypertension in Pregnancy

Study Questions:

For the management of severe hypertension in pregnancy, what is the efficacy and safety of oral labetalol, nifedipine, and methyldopa?

Methods:

Patients in two public hospitals in Nagpur, India were enrolled in this parallel-group, open-label, randomized controlled trial. Inclusion criteria were pregnant women at gestational age of ≥28 weeks with severe hypertension (systolic blood pressure ≥160 mm Hg or diastolic ≥110 mm Hg). Treatment was randomly assigned to: 10 mg nifedipine, 200 mg labetalol, or 1000 mg methyldopa. The nifedipine and labetalol treatment groups received escalated hourly medication if hypertension persisted, but the methyldopa regimen was a single dose without escalation. The primary outcome was control of blood pressure within 6 hours without adverse outcomes (defined as systolic blood pressure 120-150 mm Hg and diastolic blood pressure 70-100 mm Hg).

Results:

Of 2,307 women screened, 1,413 were excluded (ineligible, declined to participate, had impending eclampsia, in active labor, or a combination). The remaining 894 women were randomly assigned by intention-to-treat: 298 (33%) women to nifedipine, 295 (33%) women to labetalol, and 301 (33%) women to methyldopa. The primary outcome (goal blood pressure within 6 hours) was achieved most frequently in women treated with nifedipine, which was significantly more than those in the methyldopa group (249 [84%] vs. 320 [76%]; p = 0.03), but not significantly more than among women treated with labetalol (249 [84%] vs. 228 [77%]; p = 0.05). There was no significant difference between the nifedipine and labetalol groups (p = 0.80). Adverse events were uncommon: one (<1%) woman in the labetalol group had an intrapartum seizure, and six (1%) neonates were stillborn, with no significant difference among the different medications.

Conclusions:

Each of the three oral antihypertensives lowered the blood pressure adequately in most pregnant women. Nifedipine achieved the desired blood pressure more frequently than labetalol or methyldopa, but all three are viable options and may be useful in low-resource settings.

Perspective:

Hypertensive disorders of pregnancy are among the leading causes of maternal mortality worldwide. Rapid pharmacologic treatment is frequently needed to prevent adverse outcomes. Pregnant women with hypertensive urgency are often treated with intravenous (IV) labetalol or hydralazine. In resource-limited areas, IV medications can be a challenge due to lack of refrigeration, supplies, monitoring, or trained personnel. Therefore, this study directly compared three oral regimens (labetalol, nifedipine, and methyldopa) and found them each to be viable options. Nifedipine was significantly more effective than methyldopa, but nifedipine is not specifically listed by the World Health Organization (WHO) as an oral medication for the treatment of severe hypertension. In contrast, the American College of Obstetrics and Gynecology (ACOG) lists IV labetalol and hydralazine as first-line treatments, but also suggests immediate-release oral nifedipine be considered first-line, particularly when IV access is not available. Since delays in therapy can lead to adverse outcomes, rapidly initiating treatment with oral medication is important, particularly when IV access is unavailable.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Hypertension

Keywords: Antihypertensive Agents, Blood Pressure, Blood Pressure Determination, Diastole, Gestational Age, Hydralazine, Hypertension, Labetalol, Methyldopa, Nifedipine, Pregnancy, Primary Prevention, Seizures, Women


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