Cardiovascular Protection After Preeclampsia With Enalapril

Cardiovascular disease (CVD) is the leading cause of death in women worldwide, and despite declines in all other age groups, mortality rates attributed to CVD are increasing in women of childbearing age. Hypertensive disorders of pregnancy (HDP), including preeclampsia and gestational hypertension, are well-established risk factors for CVD across diverse patient populations. There is compelling evidence that the preponderance of HDP-associated CVD risk is linked to progression to chronic hypertension following pregnancy. Thus, the postpartum period after HDP is a critical yet under-studied opportunity for intervention to prevent chronic disease in women.

One intervention that may reduce the chance of progression to CVD is the institution of anti-hypertensive medications. The cornerstones of current postpartum anti-hypertensive treatment are labetalol (a dual β- and α-adrenergic receptor blocker) and nifedipine (a calcium channel blocker), primarily due to their well-documented safety profile during pregnancy and obstetricians' comfort with their dosing. However, there are significant limitations in the current standard of care for anti-hypertensive treatment postpartum, including (1) two to three times per day dosing, (2) significant side effects, and (3) lack of endothelial or cardioprotective effects. Further, there is some evidence that these medications may not be as efficacious as some others.

Angiotensin-converting enzyme (ACE) inhibitors are anti-hypertensive agents that provide cardioprotection through anti-inflammatory effects, increased nitric oxide bioavailability, and diminished fibrosis. Because of these benefits, they are recommended in non-pregnant / postpartum individuals who have heart failure or myocardial infarction to reduce cardiovascular mortality. Enalapril is a type of ACE- inhibitor that is taken daily or twice daily with minimal side effects, is a highly effective anti-hypertensive agent, and has a reassuring lactation safety profile, making it an ideal candidate for postpartum treatment after preeclampsia.

The overall objective of this application is to conduct a single-site RCT, which will enroll individuals within the institution's remote blood pressure (BP) management program, to allow the collection of key data that will inform a future NIH-funded RCT. The' central hypothesis is that an RCT evaluating enalapril versus standard-of-care treatments will be feasible, and that enalapril will improve blood pressure at 4 months after delivery. The investigators will test this hypothesis by pursuing the following specific aims:

Aim 1. Determine the feasibility of conducting a randomized controlled trial of enalapril versus current standard of care (labetalol or nifedipine) in postpartum individuals who have had a hypertensive disorder of pregnancy.

Aim 2. Determine whether enalapril versus standard of care improves blood pressure at 4 months postpartum.