Reference: N Engl J Med. 2022 Apr 2 early online
Chronic hypertension in pregnancy is associated with an increased risk of maternal and perinatal death as well as preeclampsia, placental abruption, and preterm birth or small-for gestational age. While there is a consensus for the treatment of pregnant women with severe hypertension, the best strategy for the treatment of mild chronic hypertension during pregnancy remains unclear. The recently published open-label randomized CHAP trial conducted in the United States evaluated the efficacy of an antihypertensive therapy initiated at a systolic blood pressure (SBP) ≥ 140 mm Hg or diastolic blood pressure (DBP) ≥ 90 mm Hg compared with standard treatment with initiation at either ≥ 160 mm Hg SBP or ≥ 105 mm Hg DBP. CHAP enrolled pregnant patients at less than 23 weeks’ gestation with a viable singleton fetus and a diagnosis of new or known mild chronic hypertension. Hypertension was defined as SBP ≥ 140 mm Hg, DBP of ≥ 90 mm Hg, or both, measured on at least two occasions before 20 weeks of gestation. The patients were randomized to immediate therapy initiation (active therapy group) or initiation only after an episode of severe hypertension (control group). Preferred antihypertensive agents for both groups were labetalol or nifedipine. Once initiated, the therapy target for both groups was a blood pressure lower than 140/90 mm Hg. The primary efficacy outcome was a composite of severe preeclampsia, medically indicated preterm birth occurring before 35 weeks of gestation, placental abruption, or fetal/neonatal death.
Over 29,000 pregnant patients underwent screening, many of whom did not qualify due to medical comorbidities or nonadherence to medications. Among 2,408 patients assessed at baseline, the mean age was 32 years and 47.5% identified as Black, 27.9% as White, and 20.3% as Hispanic. Fifty-six percent had prior chronic hypertension and were receiving medication, 22% had prior chronic hypertension but were not taking medication, and 22% had a new diagnosis of chronic hypertension. Ninety-six percent of the patients who completed the follow-up at six weeks after birth were included in the analysis.
The active therapy group had a lower incidence of the primary efficacy composite outcome compared with the control group (30.2% vs. 37%, p < 0.001). In particular, the incidences of preeclampsia with severe features (23.3% vs. 29.1%, p < 0.05) and medically indicated preterm birth before 35 weeks’ gestation (12.2% vs. 16.7%, p < 0.05) were significantly lower in the active therapy group, whereas abruption and fetal or neonatal death were similar in both groups. Poor fetal growth - the primary safety outcome of the trial - was not statistically different between the two groups (11.2% vs. 10.4%, p = 0.56). Analyses of the secondary outcomes suggested that active therapy may decrease the risk of severe maternal hypertension (36.1% vs. 44.2%, p < 0.05), any preeclampsia (24.4% vs. 31.1%, p < 0.05), preterm birth (27.5% vs. 31.4%, p < 0.05), and low birth weight (19.2% vs. 23.1%, p < 0.05). The total number of serious adverse events was similar in both groups (155 vs. 178).
The findings of this study differ from a prior smaller randomized trial which found targeting a lower diastolic goal did not improve patient-oriented outcomes. This larger, multicenter trial in a diverse, at-risk population has already garnered support from physician organizations. This trial does demonstrate improvement in meaningful outcomes, but we must give some consideration to limitations including lack of blinding and difficulties in generalizability given the large number of patients who did not meet inclusion criteria, such as adherence to medication at baseline. In conclusion, the CHAP trial convincingly suggests that active antihypertensive therapy for mild chronic hypertension in pregnancy reduces the risk of adverse outcomes without compromising fetal growth.For more information, see the topic Hypertensive Disorders of Pregnancy in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Vincent Lemaitre, PhD, Senior Medical Writer at DynaMed. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Katharine DeGeorge, MD, MS, Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia; Dan Randall, MD, Deputy Editor at DynaMed; Carina Brown, MD, Assistant Professor at Cone Health Family Medicine Residency; Nicole Jensen, MD, Family Physician at WholeHealth Medical; and Sarah Hill, MSc, Associate Editor at DynaMed.