Mild chronic hypertension in pregnancy: BP-lowering treatment improves outcomes without harm

When it comes to treating mild chronic hypertension during pregnancy, a strategy of lowering blood pressure (BP) below 140/90 mm Hg is preferrable, as it leads to better pregnancy outcomes without increasing the risk of birthing small-for-gestational-age babies when compared with a strategy of reserving treatment only for severe hypertension, according to the open-label Chronic Hypertension and Pregnancy (CHAP) trial.

The primary outcome of a composite of pre-eclampsia with severe features, medically indicated preterm birth at less than 35 weeks’ gestation, placental abruption, or foetal or neonatal death occurred with significantly less frequency among women who received BP-lowering medications recommended for use in pregnancy (active-treatment group, n=1,208) than among those who were not given such treatment, unless severe hypertension (≥160/≥105 mm Hg) developed (control group, n=1,208; 30.2 percent vs 37.0 percent; adjusted risk ratio [aRR], 0.82, 95 percent confidence interval [CI], 0.74–0.92; p<0.001). [N Engl J Med 2022;doi:10.1056/NEJMoa2201295]

Furthermore, the safety outcome was similar in the two treatment groups, with the rate of small-for-gestational-age birth weight below the 10th percentile for gestational age being 11.2 percent with active treatment vs 10.4 percent with control (aRR, 1.04, 95 percent CI, 0.82–1.31; p=0.76).

“The estimates of the components of the primary outcome and most secondary outcomes (including the composites of serious maternal [RR, 0.75] or neonatal [RR, 0.77] complications, pre-eclampsia [RR, 0.79], and preterm birth [RR, 0.87]) were consistent with the results of the primary analysis,” the investigators pointed out. “[About] 14 to 15 patients would need to receive active treatment to prevent one primary-outcome event.”

The investigators also noted that fewer patients who received active vs control treatment progressed to severe hypertension, which was consistent with the findings of previous trials and a systematic review of antihypertensive therapy for mild chronic hypertension in pregnancy. [BMJ 1999;318:1332-1336; Am J Obstet Gynecol 1990;162:960-966; N Engl J Med 2015;372:407-417]

However, CHAP was not powered to assess differences in treatment effects across subgroups, they acknowledged. “Additional evaluation of treatment effect in patients with newly diagnosed hypertension or a body-mass index of ≥40 kg/m² may be informative.”

CHAP included 2,416 women (average age 32 years, 48 percent Non-Hispanic Black women) with singleton foetuses at a gestational age of <23 weeks at baseline. Most of them (56 percent) had known chronic hypertension and were receiving medication, 22 percent had known chronic hypertension and were not receiving medication, and 22 percent had newly diagnosed chronic hypertension. During randomization, the patients in the active-treatment group were assigned to receive labetalol (61.7 percent) or nifedipine (35.6 percent); a few women (2.7 percent) received other medications.

Practice-changing finding?

In an accompanying editorial, Drs Michael Greene and Winfred Williams from Massachusetts General Hospital in Boston, US, found the apparent reduction in the incidence of various measures of pre-eclampsia in the active-treatment group to be the most exciting finding in CHAPS. This has not been observed in previous randomized trials, including CHIPS—a large trial that evaluated “tight versus less-tight” antihypertensive treatment in women with mild or severe chronic or pregnancy-associated hypertension. [N Engl J Med 2022;doi:10.1056/NEJMe2203388; J Am Heart Assoc 2017;6:e005526-e005526]

However, they pointed out that such finding should be interpreted with caution, as secondary outcomes were not adjusted for multiplicity.

“The consequences of hypertension in pregnancy for both mothers and their offspring are well known… Guidelines for treating hypertension in adults have been clear in recommending treatment at increasingly lower BP thresholds to minimize long-term risks of death and complications,” according to Greene and Williams. [J Am Coll Cardiol 2018;71:e127-e248]

“Early small studies of treatment of mild hypertension in pregnancy in otherwise healthy women have not shown clear or durable benefits of such treatment. These findings have caused fraught decision making due to concern about the potential unintended foetal consequences of poor growth or death from lowering of placental perfusion pressure,” they pointed out. [Obstet Gynecol 1979;53:489-494; Am J Obstet Gynecol 1990;162:960-966]

If the results of CHAP are confirmed in subsequent studies, then there would be a compelling reason to revise the recommendations for clinical practice regarding the treatment of mild hypertension during pregnancy, Greene and Williams said.