Hypertension Control During Pregnancy Validated in Large Trial

Ted Bosworth

April 02, 2022

Pregnant women with even mild hypertension should receive blood pressure–lowering medications to reduce the likelihood of adverse outcomes for the mother and the child, according to a large, open-label, randomized trial.

"Treating to the blood pressure goal in this study reduced the risk of adverse events associated with pregnancy but did not impair fetal growth," Alan T. Tita, MD, PhD, associate dean for Global and Women's Health, University of Alabama, Birmingham, reported at the annual scientific sessions of the American College of Cardiology.

The question of whether to treat chronic hypertension during pregnancy has been "an international controversy for decades," said Dr. Tita, who led the investigator-initiated Chronic Hypertension and Pregnancy (CHAP) trial.

For the composite primary outcome of severe preeclampsia, medically indicated preterm birth at less than 35 weeks of gestation, placental abruption, or fetal/neonatal death, the treatment of hypertension versus no treatment showed a relative risk reduction of 18% (30.2% vs. 37%, (hazard ratio, 0.82; < .001).

Small for Gestational Age Is Primary Safety Endpoint

An increase in preeclampsia risk in women whose fetus was small for gestational age (SGA), a theoretical consequence of reductions in arterial pressure, was not seen. The rate of SGA, defined as below the 10th percentile, was slightly higher in the treatment group (11.2% vs. 10.4%), but the difference did not approach significance (= 0.76).

By answering this long-pending question, the CHAP data are "practice changing," declared an ACC-invited commentator, Athena Poppas, MD, chief of cardiology and director of the Lifespan Cardiovascular Institute, Providence, R.I. She agreed that the need for treatment of mild chronic hypertension has been a dilemma for clinicians that is now acceptably resolved.

In this trial, 2,408 pregnant women with chronic mild hypertension defined as a blood pressure of 160/90 mm Hg were randomized to treatment with a goal blood pressure of less than 140/90 mm Hg or no treatment unless the blood pressure rose to at least 160/105. All women had singleton pregnancies. Enrollment before 23 weeks of gestation was required. Severe hypertension (at least 160/105 mm Hg) was an exclusion criterion, as were several comorbidities, such as kidney disease.

Combination Therapy Accepted for <140/90 mm Hg Goal

The beta-blocker labetalol or the calcium channel blocker nifedipine as single agents were the preferred antihypertensive medications in the protocol, but other medications were permitted. To reach the blood pressure goal, the single-agent therapy was titrated to the maximum dose before starting a second agent.

After randomization the systolic and diastolic blood pressures fell in both groups, but they fell more and remained consistently lower in the active treatment group, particularly during the first 20 weeks after randomization, according to graphs displayed by Dr. Tita. Over the course of the study, the mean diastolic blood pressures were 129.5 and 132.6 mm Hg in the active treatment and control groups, respectively, while the systolic pressures were 79.1 vs. 81.5 mm Hg.

When the components of the primary outcome were evaluated separately, the greatest advantage of treatment was the reduction in the rate of severe eclampsia (23.3% vs. 29.1%; HR, 0.80: 95% confidence interval, 0.70-0.92) and preterm birth (12.2% vs. 16.7%; HR, 0.73: 95% CI, 0.60-0.89).

Across a large array of subgroups, including those with or without diabetes and those treated before or after 14 weeks of gestation, there was a consistent advantage for treatment, even if not statistically different. It is notable that 48% of patients were Black and 35% had a body mass index of at least 40. The active treatment was favored across all groups stratified by these characteristics.

Although the incidences of placental abruption (1.7% on treatment vs. 1.9% without) and fetal or neonatal death (3.5% vs. 4.3%) were lower in the active treatment group, they were uncommon events in both arms of the study. The differences did not reach statistical significance.

Severe SGA, which was defined as below the 5th percentile, was also numerically but not significantly higher in the control arm than in the group receiving treatment (5.1% vs. 5.5%), but the incidence of composite adverse maternal events was numerically lower (2.1% vs. 2.8%). The incidences of all components of maternal morbidity, such as maternal death (0.1% vs. 0.2%) pulmonary edema (0.4% vs. 0.9%), heart failure (0.1% vs. 0.1%), and acute kidney injury (0.8% vs. 1.2%), were either lower or the same on active treatment versus no treatment.

According to Dr. Tita, who called CHAP one of the largest and most diverse studies to address the value of treating mild hypertension in pregnancy, the American College of Obstetricians and Gynecologists (ACOG) is evaluating these data for changing their current guidelines for managing hypertension during pregnancy.

"The rate of chronic hypertension during pregnancy has been rising in the United States due to the increase in the average age of pregnant women and the rising rates of obesity," Dr. Tita commented.

"We definitely needed these data," said Mary Norine Walsh, MD, medical director, Ascension Saint Vincent Cardiovascular Research Institute, Indianapolis. Not only has the value of treating mild hypertension been unresolved, but Dr. Walsh pointed out that the rates of maternal mortality in the United States are rising and now generally exceed those of many other developed countries.

There are several features in the design of this trial that make the results even more salient to clinical practice, according to Dr. Walsh. This includes the fact that about half of patients enrolled were on Medicaid. As a result, the study confirmed benefit in what Dr. Walsh characterized as a "vulnerable" population.

"We will be busy now to make sure that our [pregnant] patients are achieving these target blood pressures," Dr. Walsh said. She indicated that CHAP validates the treatment target of 140/90 mm Hg as a standard of care.

The results were published in the New England Journal of Medicine simultaneously with its ACC presentation.

The trial was funded by the National Heart, Lung, and Blood Institute. Dr. Tita reports research grants from Pfizer. Dr. Walsh reports a financial relationship with EBR Systems. Dr. Poppas reports no potential conflicts of interest.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.



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