Labetalol

Oral nifedipine, methyldopa, labetalol ‘viable initial options’ for severe hypertension in pregnancy in low-resource settings

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Comparison of the safety and efficacy of three oral antihypertensives — labetalol, nifedipine retard and methyldopa — for use in pregnant women with severe hypertension showed that each drug resulted in BP control within 6 hours, with nifedipine retard demonstrating the greatest frequency of BP control, according to data published in The Lancet.

Although typical hypertension treatments include IV medications, it may not always be a feasible method for drug delivery in pregnant women due to venous access and fetal monitoring in busy or low-income environments; therefore, oral drugs could prove to be as effective and more accessible for patients living in areas affected by these treatment disparities, according to the researchers.

Cardiology Today corresponded with Hillary Bracken, PhD, senior director at Gynuity Health Projects, regarding the implications of these findings.

“Use of oral antihypertensive agents in a structured, goal-oriented approach can effectively and safely control blood pressure in pregnant women with severe hypertension,” Bracken said. “Treatment can be initiated immediately upon diagnosis — particularly in limited resource medical environments. Initiation of therapy need not be delayed until transfer to a higher-level center and may be expected to reduce maternal morbidity.”

In the multicenter, parallel-group, open-label, randomized, controlled trial, researchers compared the safety and efficacy of nifedipine, labetalol and methyldopa at two public hospitals in Nagpur, India. Treatment eligible patients (n = 894) were aged at least 18 years, pregnant with fetuses gestated at least 28 weeks, required pharmacological BP control for severe hypertension and were able to swallow oral medication.

Women with severe hypertension were randomly assigned to receive one of the three drugs: 298 received nifedipine, 295 received labetalol and 301 received methyldopa. Treatment was initiated between April 1, 2015, and Aug. 21, 2017. The primary outcome was BP control, defined as 120 to 150 mm Hg systolic BP and 70 to 100 mm Hg diastolic BP within 6 hours, with no adverse events.

Researchers found that the primary outcome was more common in pregnant women who received nifedipine retard compared with those who received methyldopa (84% vs. 76%; P = .03). There was no difference in the primary outcome between the nifedipine and labetalol groups (84% vs. 77%; P = .05) and the labetalol and methyldopa groups (P = .8).

“We anticipated a significant level of maternal complications. [We] were surprised to find very low rates of maternal morbidity in each arm, including a single eclamptic seizure despite a low rate of magnesium sulfate (MgSO4) utilization.,” Bracken said. “[Additionally], we were surprised to find a higher rate of NICU utilization in the nifedipine arm despite equivalent birth weights and gestational ages.”

According to the results, seven (1% of births) adverse events occurred during the course of the study. One woman in the labetalol group had an intrapartum seizure and six neonates (one in the nifedipine group, two in the labetalol group and three in the methyldopa group) were stillborn.

“[Intensive] care unit admissions were significantly more frequent in the nifedipine group,” the authors wrote. “More neonates born to women in the nifedipine group were admitted to the intensive care unit because they had a low or very low birthweight compared with those born to women in the methyldopa or labetalol groups.”

“Infants in all groups were exposed to comparable prematurity,” Thomas Easterling, MD, director of the maternal hypertension clinic at the University of Washington School of Medicine, told Cardiology Today. “Birth weights and gestational ages at birth were not different between groups.  More babies in the nifedipine group required admission for their low birth weight, their admitting diagnosis.  It seems that in a more or less equivalent cohort, the small babies in the nifedipine group received more attention.”

These findings have implications in low-resource settings, as use of the oral antihypertensives studied is common and recommended by the WHO for treatment of severe hypertension in pregnancy.

“In low-resource settings, including some basic obstetrical facilities in the United States, oral treatment of severe hypertension in pregnancy can be initiated immediately, during triage for more definitive care,” Bracken told Cardiology Today. – by Scott Buzby

Labetalol may be best option for pregnant women with hypertension

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Among antihypertensive medications commonly prescribed for pregnant women, all reduced risk for severe hypertension, but labetalol also reduced odds of other poor outcomes, researchers reported.

Jeffrey N. Bone, MS, statistician and PhD candidate in the department of obstetrics and gynecology at the University of British Columbia in Vancouver, Canada, and colleagues conducted a systematic review and meta-analysis of 61 trials covering 6,923 pregnant women to determine which antihypertensive medications were best for controlling nonsevere hypertension.

pregnant woman with pills

Outcomes of interest included severe hypertension, proteinuria/preeclampsia, fetal/newborn death, small for gestational age infants and admission to neonatal care.

The commonly prescribed antihypertensive medications analyzed were labetalol, other beta-blockers, methyldopa, calcium channel blockers and mixed/multidrug therapy, and all reduced risk for severe hypertension by 30% to 70% compared with placebo or no therapy, Bone and colleagues wrote.

Compared with placebo or no therapy, labetalol was associated with reduced odds of proteinuria/preeclampsia (OR = 0.73; 95% credible interval [CrI], 0.54-0.99) and fetal/newborn death (OR = 0.54; 95% CrI, 0.3-0.98), the researchers wrote.

Compared with methyldopa (OR = 0.66; 95% CrI, 0.44-0.99) and calcium channel blockers (OR = 0.63; 95% CrI, 0.41-0.96), labetalol was associated with reduced odds of proteinuria/preeclampsia, according to the researchers.

Bone and colleagues found no significant differences for any other therapy in any other outcome, but noted the credible intervals were wide.

When the researchers conducted a trial sequential analysis, they determined that definitive evidence would require 2,500 to 10,000 women per arm for severe hypertension and safety outcomes and 15,000 women per arm for fetal/newborn death.

“It is unsurprising that antihypertensive therapy outperforms, by a large margin, placebo/no therapy in lowering BP. Many national and international guidelines now recommend that practitioners offer antihypertensive therapy to women to normalize BP in pregnancy,” Bone and colleagues wrote. “Notwithstanding neonatal concerns, it may be reasonable to recommend first-line therapy with labetalol, given the additional potential benefits of reduced proteinuria/preeclampsia and perinatal death.”