Hypertension in pregnancy: Labetalol extends benefits for pregnancy outcomes

Common blood pressure (BP)-lowering medications in pregnancy cut the risk of severe hypertension, but labetalol has the added advantage of reducing the risks of proteinuria or pre-eclampsia and perinatal death, according to the results of a network meta-analysis.

Pooled data from 61 trials of antihypertensives for nonsevere pregnancy hypertension (n=6,923 women) showed that all commonly prescribed BP lowering drugs (labetalol, other β-blockers, methyldopa, calcium channel blockers, and mixed/multidrug therapy) produced around 30–70 percent reduction in the risk of progressing to severe hypertension as compared with placebo or no therapy. [Hypertension 2022;79:614-628]

There was no indication that one drug, whether used alone or in combination, was different from another with regard to preventing progression to severe hypertension, the investigators noted.

Meanwhile, labetalol was the sole BP-lowering drug to yield a beneficial effect on maternal and perinatal outcomes. Its use lowered the likelihood of proteinuria/pre-eclampsia by 27 percent (odds ratio [OR], 0.73, 95 percent credible interval [CrI], 0.54–0.99) and foetal/newborn death by 46 percent (OR, 0.54, 95 percent CrI, 0.30–0.98) compared with placebo or no therapy.

When compared with other drugs, the odds of proteinuria/pre-eclampsia decreased by more than 30 percent with labetalol vs methyldopa (OR, 0.66, 95 percent CrI, 0.44–0.99) and calcium channel blockers (OR, 0.63, 95 percent CrI, 0.41–0.96).

No other differences were identified, although credible intervals were wide, the investigators acknowledged. “Trial sequential analysis indicated that 2,500 to 10,000 women per arm (severe hypertension or safety outcomes) to >15,000 per arm (foetal/newborn death) would be required to provide definitive evidence.”

Suitable first-line therapy

That BP-lowering drugs outperform placebo/no therapy by a large margin does not come as a surprise, according to the investigators. In fact, many national and international guidelines now recommend that clinicians prescribe antihypertensives to women to normalize BP in pregnancy. [Am J Obstet Gynecol 2020;doi:10.1016/j.ajog.2020.08.018]

“Our findings are consistent with traditional meta-analysis that has refuted an association between β-blockers and foetal growth restriction. Notwithstanding, concerns about atenolol remain; this drug was not analysed separately from β-blockers in [the present analysis] but was in another that examined antihypertensives for treatment of chronic hypertension in pregnancy, showing an association with small for gestational age (SGA),” the investigators said. [Am J Obstet Gynecol 2020;223:525-537]

“[Despite the] neonatal concerns, it may be reasonable to recommend first-line therapy with labetalol, given the additional potential benefits of reduced proteinuria/pre-eclampsia and perinatal death,” they noted. [https://www.nice.org.uk/guidance/ng133] 

Other reasonable choices include β-blockers, calcium channel blockers, labetalol, methyldopa, or multi-drug therapy. These choices, according to the investigators, increase the possibility that a hypertensive pregnant woman, regardless of the care setting, will have access to a BP-lowering drug.

The study has several limitations, such as the inclusion of >20-year-old trials. Just the same, the present data suggest that “clinicians can individualize antihypertensive therapy in pregnancy by choosing from among those most commonly recommended until comprehensive information can be gathered from real-world care,” the investigators said.