Enalapril for cardiovascular protection after preeclampsia

The National Heart, Lung, and Blood Institute awarded Women & Infants Hospital of Rhode Island $244,569 on July 15, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to conduct a single-site randomized controlled trial piloting the feasibility and efficacy of postpartum enalapril treatment for cardiovascular protection in women with a history of preeclampsia.

The trial will enroll women within the hospital's remote blood pressure management program to assess whether enalapril, an angiotensin-converting enzyme inhibitor with cardioprotective properties, can reduce adverse cardiac remodeling and improve blood pressure control beyond standard postpartum hypertension management. Preeclampsia is a well-established cardiovascular disease risk factor, yet currently no evidence-based pharmacologic interventions specifically target this at-risk population postpartum. The research addresses cardiovascular disease mortality, which is increasing in women of childbearing age despite declines in other age groups. The two specific aims are to pilot test the feasibility of conducting a randomized controlled trial of postpartum enalapril versus standard of care, and to assess enalapril's effect on blood pressure and cardiac remodeling at four months after delivery. Data collected will inform a future larger NIH-funded trial.

The award period runs from July 15, 2026, through June 30, 2028. Work is performed in Providence, Rhode Island.

Abstract

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. Preeclampsia is a well-established risk factor for CVD across all americans, however, there are currently no evidence-based interventions targeting this at-risk patient population. While blood pressure control is the cornerstone of postpartum management, emerging evidence suggests that management of hypertension alone does not fully mitigate CVD risk after preeclampsia. The overall goal of this line of research is to begin to develop and test novel pharmacologic interventions for postpartum management following preeclampsia, representing a paradigm shift focused on cardiovascular recovery postpartum in addition to blood pressure control. Angiotensin-converting enzyme inhibitors, including enalapril, are anti-hypertensive agents that provide cardioprotection through anti-inflammatory effects and diminished fibrosis, and importantly, are recommended in non-pregnant or postpartum people with heart failure to reduce cardiovascular morbidity. In this R03 application, the objective is to conduct a single-site randomized clinical trial (RCT), which will enroll women within our institution's remote blood pressure management program, to allow the collection of key data that will inform a future NIH-funded RCT through two specific aims: (1) to pilot test the feasibility of conducting a randomized controlled trial of postpartum enalapril VS. Standard of care, and 2) to assess the effect of postpartum enalapril on blood pressure and cardiac remodeling. Our central hypothesis is that an RCT evaluating enalapril versus standard-of-care treatments will be feasible, and that enalapril will improve blood pressure and reduce adverse cardiac remodeling at 4 months after delivery. The research proposed in this application is innovative in its novel adaptation of an evidence-based, safe strategy to improve postpartum blood pressure and cardiac remodeling in an understudied population with significant morbidity during a critical time period. This proposal is significant as IT will provide an opportunity to assess the feasibility and explore the effect of enalapril on cardiac function in addition to blood pressure. Effective interventions to improve postpartum hypertension care and reduce long-term cardiovascular risk have broad implications for improving maternal morbidity and reducing disparities in care. In conjunction with my K23 award, the findings from this R03 application will provide a valuable framework to inform subsequent large-scale randomized trials of pharmacologic interventions in the postpartum period following preeclampsia. Successful completion of this line of research would represent a transformation in postpartum management of women with preeclampsia and have a direct impact to improve hypertension and cardiovascular-related maternal morbidity and mortality in the united states.