Treatment of Chronic Hypertension during Pregnancy: Is it time to be more aggressive?

Treatment of Chronic Hypertension during Pregnancy: Is it time to be more aggressive?
Sandra Leo, PharmD, Mille Lacs Health System

Background: Chronic hypertension during pregnancy, defined by the American College of Gynecology (ACOG) as hypertension diagnosed before pregnancy or during pregnancy before 20 weeks of gestation, is associated with many maternal and fetal risks. Per a 2019 American Heart Association (AHA) study, as many as 1.5% of pregnancies in the United States are affected by this condition and that percentage continues to rise. Maternal hypertension during pregnancy presents risk for cerebrovascular accidents, gestational diabetes, postpartum hemorrhage, maternal mortality, low birth weight, preterm births, and congenital anomalies independent of subsequent additional risk for progression to preeclampsia. However, recommendations for when to initiate treatment and how aggressive to be varies widely across international guidelines due to lack of studies in this population, concern for low-birth weight due to reduced placental perfusion caused by antihypertensives, and potential fetal risk due to in-utero exposure to these medications.

Evidence: Current treatment recommendations are focused primarily on preventing progression to severe hypertension. A 2014 Cochrane Review of 49 trials demonstrated that treatment of mild to moderate hypertension during pregnancy did result in reduced risk of progression to severe hypertension, but showed no confirmed benefit to fetal/maternal outcomes or impact on development of preeclampsia. The 2015 Control of Hypertension in Pregnancy Study, which compared tight hypertension control during pregnancy (diastolic blood pressure target of <85 mm Hg) to less tight control (diastolic blood pressure target of <100 mm Hg), found a similar lack of evidence for benefits to fetal and maternal outcomes. An ACOG 2019 practice bulletin recommended initiation of antihypertensive treatment for persistent systolic blood pressures >160 mm Hg and/or diastolic blood pressures >110 mm Hg. However, other international organizations, including the International Society for the Study of Hypertension in Pregnancy, recommend initiation of treatment for persistent systolic blood pressures >140 mm Hg and/or diastolic blood pressures >90 mm Hg.

New evidence suggests that tighter blood pressure control in pregnancy is more beneficial than what has previously been shown. The Chronic Hypertension and Pregnancy (CHAP) study, a large, multi-center, randomized control trial, sought to clarify when to initiate antihypertensives in pregnant women. This study enrolled 2,408 participants with a singleton pregnancy and a known or confirmed diagnosis of hypertension before 23 weeks of gestation (as defined by a systolic blood pressure >140 mm Hg and/or diastolic blood pressure >90 mm Hg measured twice at least four hours apart). Exclusion criteria included severe hypertension (as defined by a systolic blood pressure >160 mm Hg and/or diastolic blood pressure >105 mm Hg measured twice at least four hours apart), requirement of more than one antihypertensive medication at initiation, multiple fetuses, contraindications to nifedipine or labetalol, and other concurrent conditions that increased fetal or maternal risk. Participants were randomized to a target blood pressure of <140/90 mm Hg with antihypertensive medications or a standard treatment where antihypertensive medications were only initiated at a blood pressure of >160/105 mm Hg. First line treatment involved nifedipine extended-release and/or labetalol, although amlodipine or methyldopa was also used per patient preference. Tighter blood pressure control showed statistically significant decreases in development of preeclampsia (RR 0.79 [95% CI 0.69 - 0.89]), preterm births (RR 0.87 [95% CI 0.77-0.99]), and development of maternal severe hypertension (RR 0.82 [95% CI 0.74 - 0.90]), as well as statistically significant increases in birth weight (RR 0.83 [95% CI 0.71-0.97]). However, no statistically significant differences were seen in other safety endpoints including maternal death, cesarean deliveries, or maternal blood transfusions.

Discussion & Clinical Impact: Healthcare providers should recognize that hypertensive risk in pregnancy lies outside just the risk for development of preeclampsia. Chronic hypertension during pregnancy is also associated with progression of Atherosclerotic Cardiovascular Disease (ASCVD) later in life, in addition to adverse peripartum maternal and fetal outcomes. The CHAP trial lends support to organizational recommendations that advocate for stricter blood pressure control in pregnant women given the evidence that blood pressure management improves maternal and pregnancy outcomes, while preventing development of preeclampsia and severe hypertension. Further studies are needed to delineate this role in improving maternal and fetal ASCVD outcomes, as well as determining optimal antihypertensive treatment strategies for this condition.

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