Treating Patients With Mild Hypertension During Pregnancy Improves Outcomes: The Chronic Hypertension and Pregnancy (CHAP) Trial

AUTHOR:
Michael J. Bloch, MD
Associate Professor, University of Nevada School of Medicine
Medical Director, Vascular Care, Renown Institute for Heart and Vascular Health
President, Blue Spruce Medical Consultants, PLLC
Reno, Nevada

CITATION:
Bloch MJ. Treating patients with mild hypertension during pregnancy improves outcomes: the Chronic Hypertension and Pregnancy (CHAP) study. Consultant360. Published online July 29, 2022.

The risks and benefits of treating patients with mild to moderate hypertension during pregnancy have been uncertain for decades. In fact, cardiovascular specialists and obstetricians have even been at odds over what they consider “mild” hypertension. In general, because of previous data that suggested treatment of mild hypertension may lead to worse fetal outcomes, obstetricians have generally targeted less-aggressive blood pressure (BP) goals than cardiovascular specialists during pregnancy.¹ The Chronic Hypertension and Pregnancy (CHAP) trial was, therefore, designed to determine whether targeting a BP of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal outcomes.

CHAP was an open-label, multicenter, randomized clinical trial that randomly assigned patients with a known or new diagnosis of hypertension at a gestational age of less than 23 weeks to either active pharmacological therapy with a BP target of less than 140 mm Hg systolic and less than 90 mmHg diastolic or no treatment (including stopping the medication if needed) unless BP rose to either at least 160 mm Hg systolic or 105 mm Hg diastolic.² Exclusion criteria included severe antihypertension or hypertension requiring more than one medication at baseline, known secondary hypertension, multiple fetuses, and contraindications to “first-line” medications commonly used for hypertension in pregnancy.

 Patients in the active-therapy group were prescribed labetalol, extended-release nifedipine, or rarely amlodipine or methyldopa at the discretion of the investigator, and the dose of medication was escalated if BP was higher than 140/90 mm Hg. The control group received medication only if BP exceeded 160/105 mm Hg. The primary efficacy outcome was defined as a composite of preeclampsia with severe features, medically indicated preterm birth before 35 weeks gestation, placental abruption, or fetal or neonatal death. The primary safety outcome was poor fetal growth defined as a birth weight less than the 10th percentile. Numerous secondary maternal and fetal outcomes were also prespecified, and multiple subgroup comparisons were prespecified including whether hypertension was previously diagnosed before pregnancy or newly diagnosed at the time of pregnancy.

Overall, 2419 women were randomly assigned, with a majority (78%) having known chronic hypertension at baseline. Most participants (56%) were taking BP medications at the time when they were randomly assigned (mostly nifedipine and labetalol). Non-Hispanic Black women made up 48% of the study population, Hispanic women made up 20%, and non-Hispanic White women make up 28%.

Expectedly, the mean achieved BP over the course of the trial was lower in the active treatment group (129.5/79.1 mm Hg vs 132.6/81.5 mm Hg). In total, the active treatment group had an 18% reduction in the rate of the primary efficacy endpoint with a number needed to treat (NNT) to prevent one primary outcome of 14.7. More specifically, the risk of preeclampsia with severe features was 20% lower in the active treatment group, and the risk of preterm birth before 35 weeks was 27% lower in the active treatment group. Additionally, severe maternal hypertension without preeclampsia and preeclampsia without severe features were significantly less common in the actively treated group. In terms of safety, there was no significant difference in the incidence of low birth rate or any other adverse fetal outcomes between groups.

In summary, in pregnant women with mild to moderate hypertension at baseline, active treatment with a BP target of less than 140/90 mm Hg was associated with significantly better maternal outcomes than a control strategy of no antihypertensive treatment unless BP was greater than 160/105 mm Hg without causing adverse fetal outcomes. Event rates were high, and the NNT to prevent these important adverse clinical outcomes—preeclampsia with and without severe features and severe hypertension leading to premature delivery—was clinically meaningful. Additionally, these benefits were seen despite the fact that the achieved BP in both the active treatment (129/79 mm Hg) and control groups (132/81 mm Hg) were lower than expected.

Taken together, these findings should give clinicians, regardless of specialty, confidence in treating patients with hypertension during pregnancy with at least one medication. Of course, there are important caveats to keep in mind, including the fact that this trial excluded patients with more severe hypertension or those requiring more than one medication at baseline. The trial investigators used labetalol or extended-release nifedipine monotherapy almost exclusively, and as such, the results should not be generalized to other antihypertensive medications. Finally, most patients in the CHAP trial were taking low-dose aspirin by the time of delivery, which has also been shown to reduce the risk of preeclampsia in higher-risk women.

References:

1. Magee LA, Singer J, von Dadelszen P; CHIPS Study Group. Less-tight versus tight control of hypertension in pregnancy. N Engl J Med. 2015;372(24):2367-2368. doi:10.1056/NEJMc1503870
2. Tita AT, Szychowski JM, Boggess K, et al; Chronic Hypertension and Pregnancy (CHAP) Trial Consortium. Treatment for mild chronic hypertension during pregnancy. N Eng J Med. 2022;386(19):1781-1792. doi:10.1056/NEJMoa2201295