CHAP

Incomplete

Tita AT, et al. "Treatment for mild chronic hypertension during pregnancy". The New England Journal of Medicine. 2022. 386(19):1781-1792.
PubMed • Full text • PDF • ClinicalTrials.gov

Clinical Question

In pregnant patients with chronic hypertension, does treatment of hypertension with a blood pressure goal of less than 140/90 vs. 160/105 reduce the risk of preeclampsia with severe features, medically preterm birth before 35 weeks, placental abruption, or fetal or neonatal death?

Bottom Line

Treatment of chronic hypertension in pregnancy with a goal of less than 140/90 reduces the risk of preeclampsiia with severe features and medically indicated preterm birth <35 weeks compared to a blood pressure goal of 160/105, without an increased risk small for gestational age births.

Major Points

Treatment of severe range hypertension in pregnancy (ie, >160 systolic or >105-110 diastolic) has been shown to have maternal benefit, however, early small studies of treatment of mild hypertension in pregnancy did not show clear benefit. The CHIPS trial demonstrated that blood pressure control in pregnancy to a target of <85 diastolic vs. a target of <100 diastolic did not significantly improve a composite outcome of pregnancy loss or high-level neonatal care for 48 hours. A concern with treatment of mild hypertension in pregnancy is that it may lead to intrauterine growth restriction, and the CHIPS trails was not powered to assess this question.

The Chronic Hypertension and Pregnancy (CHAP) trial randomized 2,408 women with singleton pregnancies and chronic hypertension with blood pressure <160/105 to either a treatment group (prescribed antihypertensives to goal blood pressure <140/90) or control group (no blood pressure intervention unless blood pressure rises to >106/105). At a follow up of 6 weeks following birth, CHAP showed a reduction in the composite outcome of preeclampsia with severe features occurring up 2 weeks after birth, medically indicated preterm birth <35 weeks' gestation, placental abruption, or fetal or neonatal death in the treatment group vs. the control group (30.2% vs. 37.0%; RR 0.82; 95% CI 0.73-0.92; P<0.001), without a significant difference in small for gestational age neonates at <10th percentile (11.2% vs. 10.4%; RR 1.07; 95% CI 0.85-1.36; P=0.56)) and <5th percentile (5.1% vs. 5.5%; RR 0.92; 95% CI 0.65-1.30; P=0.63))

Following the publication of the CHAP trial, the Society for Maternal-Fetal Medicine and the American College of Obstetrics and Gynecology released guidance recommending treatment of mild chronic hypertension in pregnancy to a goal of <140/90.

Guidelines

ACOG Clinical Guidance for the Integration of CHAP Findings (2022)

• 140/90 as threshold for initiation and goal for titration of antihypertensive medication in chronic hypertension in pregnancy

SMFM Statement Following CHAP Trial (2022)

• Treatment for chronic hypertension in pregnancy with goal blood pressure <140/90

Design

• Multicenter, open-label, randomized controlled trail
• N=2,408
  • Active treatment (n=1208)
  • Control (n=1200)
• Setting: 70 recruiting sites in the United States
• Enrollment: September 2015 to March 2021
• Follow-up: Until 6 weeks after birth
• Analysis: Intention-to-treat
• Primary outcome: composite of preeclampsia with severe features occurring up 2 weeks after birth, medically indicated preterm birth <35 weeks' gestation, placental abruption, or fetal or neonatal death
  • Notably, blood pressure of 160/100 or greater without signs/symptoms of preeclampsia, proteinuria, or lab abnormalities did not qualify as a diagnosis preeclampsia with severe features

Population

Inclusion Criteria

• Viable singlton pregnancy at less than 23 weeks' gestation
• History of chronic hypertension or new diagnosis of chronic hypertension prior to 20 weeks' gestation

Exclusion Criteria

• Blood pressure ≥160 systolic or ≥105 diastolic
• Treatment with >1 antihypertensive medication
• Known secondary hypertension
• Multiple fetal gestation
• Contraindications to labetalol or nifedipine
• Substance abuse disorder
• Presence of high-risk comorbidities:
  • Diabetes mellitus with end organ damage
  • Diabetes mellitus diagnosed ≥20 years ago or diagnosed ≤age 10
  • Chronic kidney disease, including Cr >1.2 or protein/creatinine ratio >0.3
  • History of stroke
  • Sickle cell disease
  • Coronary artery disease
  • Angina
  • Cardiomyopathy

Baseline Characteristics

From treatment group

• Demographics: age 32.3, non-Hispanic White 28.7%, non-Hispanic Black 47.5%, Hispanic 19.7%, Government-assisted insurance or Medicaid 55.7%, private insurance 38.0%
• Systolic blood pressure 134.3
• Diastolic blood pressure 83.9
• Type of chronic hypertension:
  • New diagnosed: 21.8%
  • Diagnosed and receiving medication: 56.0%
  • Diagnosed and not receiving medication: 22.2%
• Lifestyle factors and comorbidities: current smoker 7.6%, diabetes mellitus 15.8%

From control group

• Demographics: age 32.3, non-Hispanic White 27.2%, non-Hispanic Black 47.5%, Hispanic 20.8%, Government-assisted insurance or Medicaid 54.7%, private insurance 38.6%
• Systolic blood pressure 133.7
• Diastolic blood pressure 83.4
• Type of chronic hypertension:
  • New diagnosed: 21.5%
  • Diagnosed and receiving medication: 56.8%
  • Diagnosed and not receiving medication: 21.8%
• Lifestyle factors and comorbidities: current smoker 6.8%, diabetes mellitus 15.8%

Interventions

• Randomized to blood-pressure goal with treatment to goal of less than 140/90 (active treatment) or less than 160/105 (standard therapy)
• Treatment to with labetalol or extended release nifedipine
  • Could be treated with amlodipine or methyldopa if preferred by patient
• Second medication added if needed to achieve blood pressure goal

Outcomes

Comparisons are blood pressure goal 140/90 vs. 160/105

Primary Outcomes

Composite primary outcomes

30.2% vs. 37.0% (RR 0.82; 95% CI 0.73-0.92; P<0.001)

Individual outcomes in the composite outcome

Preeclampsia with severe features

23.3% vs. 29.1% (RR 0.80; 95% CI 0.70-0.92)

Medically indicated preterm birth at <35 weeks

12.2% vs. 16.7% (RR 0.73; 95% CI 0.60-0.89)

Placental abruption

1.7% vs. 1.9% (RR 0.90; 95% CI 0.49-1.64)

Fetal or neonatal death at <28 days

3.5% vs. 4.3% (RR 0.81; 95% CI 0.54-1.21)

Safety Outcomes

Small for gestational age <10th percentile

11.2% vs. 10.4% (RR 1.07; 95% CI 0.85-1.36; P=0.56)

Small for gestational age <5th percentile

5.1% vs. 5.5% (RR 0.92; 95% CI 0.65-1.30; P=0.63)

Subgroup Analysis

Subgroup analysis was performed using patient race, presence of diabetes at baseline, gestational age <14 weeks or ≥14 weeks, and BMI. Overall, analysis of each subgroup was concordant with overall results, with exception of BMI ≥40 and patients newly diagnosed with chronic hypertension where the 95% CI were close to 1.0.

Adverse Events

• There were no significant differences between the two groups in maternal death, heart failure, stroke, pulmonary edema, ICU admission rate, intubation rate, renal failure, encephalopathy, or blood transfusion.

• There were no significant differences between the two groups in neonatal necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, grade 3 or 4 intraventricular hemorrhage, receiving respiratory support, or NICU admission rate.

Criticisms

• Unblinded study
• Large ratio of screening to enrolled patients (29,772 screened, 2408 enrolled)

Funding

National Heart, Lung, and Blood Institute