Spironolactone to Improve Pregnancy-Associated Hypertension Trajectories

The hypertensive disorders of pregnancy (HDP, e.g., gestational hypertension and preeclampsia) are a leading cause of maternal and infant morbidity and mortality and are associated with increased long-term risk of maternal atherosclerotic cardiovascular disease (CVD) and heart failure. The American College of Cardiology and American Heart Association now recognize the HDP as a sex-specific CVD risk factor to guide prescription of preventive statin therapy. Beyond this focused recommendation, however, targeted strategies for CVD risk reduction in women with HDP are not yet established. Maternal overweight/obesity is a risk factor for accelerated progression from HDP to chronic hypertension, a key mediator of heightened long-term CVD risk in women with a history of HDP, and for adverse cardiac remodeling in pregnancy. Recent preclinical evidence suggests that the HDP induce heightened vascular smooth muscle cell mineralocorticoid receptor (MR) sensitivity that persists postpartum, promoting chronic hypertension and CVD. In addition, the recent POP-HT trial suggested that blood pressure control in the very early postpartum period has long-lasting effects on the risk of chronic hypertension and cardiac remodeling in women after HDP. Integrating these lines of evidence, the investigators hypothesize that short-term pharmacologic blockade of the MR in the early postpartum period after HDP will yield long-term maternal cardiovascular benefits in women with overweight/obesity. To test this hypothesis, the investigators will compare a strategy of adding low-dose spironolactone, a breastfeeding-compatible MR antagonist, or placebo to usual care for 3 months following delivery with HDP. This multi-site trial will randomize 204 women with HDP and pre-pregnancy overweight/obesity delivering at Massachusetts General Hospital, Brigham and Women's Hospital, and the University of Pittsburgh-Magee Womens Hospital. The investigators will test the effect of short-term adjunctive postpartum spironolactone on 24-hour ambulatory blood pressure (Aim 1) and postpartum cardiac remodeling by echocardiography (Aim 2) at 9 months postpartum (i.e., 6 months after completion of study treatment).

• Left ventricular relative wall thickness (main echocardiographic outcome) [Срок оценки: Baseline and 36 weeks]
• Mean 24-hour ambulatory systolic blood pressure [Срок оценки: 36 weeks]
• Mean diurnal ambulatory systolic blood pressure [Срок оценки: 36 weeks]
• Mean diurnal ambulatory diastolic blood pressure [Срок оценки: 36 weeks]
• Mean nocturnal ambulatory systolic blood pressure [Срок оценки: 36 weeks]
• Mean nocturnal ambulatory diastolic blood pressure [Срок оценки: 36 weeks]
• Measured systolic blood pressure [Срок оценки: Baseline, 2 weeks, 12 weeks, and 36 weeks]
• Measured diastolic blood pressure [Срок оценки: Baseline, 2 weeks, 12 weeks, and 36 weeks]
• Readmission for hypertension [Срок оценки: Through study completion (36 weeks post-randomization)]
• All-cause readmission [Срок оценки: Through study completion (36 weeks post-randomization)]
• Daily defined doses of antihypertensive medication [Срок оценки: Baseline, 2 weeks, 12 weeks, and 36 weeks]
• Time to discontinuation of all non-study drug antihypertensive medications [Срок оценки: Through study completion (36 weeks post-randomization)]