Cardiac Effects of Mineralocorticoid Receptor Antagonism After Preeclampsia

Inclusion criteria

• Female with a history of preeclampsia (defined by ACOG criteria) in a singleton pregnancy without pre-gestational chronic hypertension.
• Current chronic hypertension (stage 1 or greater).
• Evidence of concentric left ventricular (LV) remodeling, defined as relative LV wall thickness \>0.42, with or without LV hypertrophy.
• Age 18-65 years at time of randomization.

Exclusion criteria

• Use of a mineralocorticoid receptor antagonist (MRA) or amiloride within the past 3 months or more than 30 days within the previous 12 months.
• Planned pregnancy, current pregnancy, or lactation.
• Systolic BP \>150 mmHg and/or diastolic BP \>95 mmHg while on antihypertensives, or systolic BP \>160 mmHg and/or diastolic BP \>100 mmHg if untreated.
• BMI \>45 kg/m².
• Clinical atherosclerotic cardiovascular disease, including coronary, cerebrovascular, or peripheral artery disease.
• Diabetes mellitus.
• LV ejection fraction \<40% or history of clinical heart failure (reduced or preserved ejection fraction).
• Hypertrophic or other genetic cardiomyopathy.
• Any moderate or greater valvular heart disease.
• eGFR \<60 mL/min/1.73 m².
• Urine microalbumin/creatinine ratio \>300 mg/g at screening.
• Abnormal electrolytes, hemoglobin, liver function tests, or TSH at screening or baseline.
• Plasma renin activity \<1 mg/mL/hour and aldosterone \>20 ng/dL (suggestive of primary aldosteronism).
• Use of oral contraceptives, progestin depot or implant (note: progestin-containing IUD is permitted), or menopausal hormone therapy.
• History of hypersensitivity or intolerance to calcium channel blockers, thiazides, or MRAs.
• Active substance abuse.
• Other serious medical illnesses or concerns about protocol adherence/mortality risk within 15 months.
• Participation in another interventional clinical study.
• Participants using GLP-1 receptor agonists (GLP-1RA) are eligible only if they have received continuous treatment with the same GLP-1RA agent at an unchanged maintenance dose for ≥12 months prior to enrollment. Dose changes, agent switches, or formulation changes within the 12 months preceding enrollment are not permitted. Temporary interruptions of ≤4 consecutive weeks (e.g., due to supply issues or procedural holds) are allowed, provided the same agent and dose are resumed. At the time of enrollment, there must be no planned or anticipated GLP-1RA dose escalation, dose reduction, or discontinuation. Initiation of GLP-1RA therapy after randomization is not permitted. Dose changes during follow-up are discouraged unless clinically required.
• Use of allopurinol.
• Use of lithium.