Enalapril may lessen long-term CVD risk after pre-eclampsia

Women with preterm pre-eclampsia can look forward to a better cardiovascular health after childbirth, with a recent study showing that postnatal use of enalapril has the potential to improve left ventricular (LV) diastolic function and remodeling, according to the results of the PICk-UP* study.

Touted as the first of its kind, PICk-UP confirmed the acceptability and feasibility of modifying postnatal cardiovascular dysfunction in women with pre-eclapmtic pregnancies requiring delivery before 37 weeks’ gestation using a postnatal intervention. This highest-risk group is said to have an eightfold risk of death from future cardiovascular disease (CVD).

“Recruitment was achieved 12 months ahead of target and uptake to the study was good (71 percent of eligible women). Nevertheless, there was a high noncompletion rate (33 percent), largely attributable to unmodifiable postnatal factors,” the investigators said. “Recruitment to completion rate was 2.2 eligible women per month.”

Importantly, postnatal enalapril treatment produced improvements in echocardiographic measurements, they added. “These early improvements have the potential to reduce long-term CVD risk.”

In the study, 60 women (mean age, 32.7 years; 22 percent Asian; median body mass index, 27.7 kg/m²) were equally randomized to postnatal treatment with enalapril or placebo for 6 months. Enalapril dose was titrated as follows: 5 mg once daily for a week, then 10 mg for 2 weeks, then 20 mg maintenance dose.

Most women (88 percent) had diastolic dysfunction and/or concentric remodeling/hypertrophy (68 percent) at baseline. After 6 months of treatment, neither total vascular resistance (p=0.59) nor systolic function (global longitudinal strain: p=0.14) improved significantly with enalapril.  [Hypertension 2020;doi:10.1161/HYPERTENSIONAHA.120.15875]

However, active treatment favourably altered diastolic function (E/E′ [the ratio of early mitral inflow velocity and early mitral annular diastolic velocity]: p=0.04) and left ventricular remodeling (relative wall thickness: p=0.01; left ventricular mass index: p=0.03) compared with placebo.

Urinary enalapril was detectable in 85 percent and 63 percent of women at 6 weeks and 6 months, respectively.

“These findings highlight the potential to use obstetric history to target intervention to improve maternal cardiovascular health in the postnatal period,” according to the investigators.

“All women [who completed the study] said they would be interested in taking [enalapril] in the future if it was found to be effective,” they said.

The investigators called for a definitive, multicentre randomized controlled trial to establish the role of enalapril in reducing the risk of CVD among women who experience preterm pre-eclampsia.

*Postnatal Enalapril to Improve Cardiovascular Function Following Preterm Preeclampsia