Long-Term Cardiovascular Risks in Patients with Hypertensive Disorders of Pregnancy Treated with Nifedipine or Labetalol

Hypertensive disorders of pregnancy (HDP) are established precursors to future cardiovascular disease. Current guidelines endorse labetalol, nifedipine, and methyldopa as first-line antihypertensive therapies, but data on long-term maternal cardiovascular risk are limited. We evaluated five-year postpartum outcomes of HDP patients who were exposed to nifedipine or labetalol during pregnancy. We conducted a retrospective cohort study using the TriNetX US Collaborative Network. Patients were identified using ICD-10-CM codes for HDP—excluding those with pre-existing hypertension-and categorized by treatment with labetalol or nifedipine. Patients exposed to amlodipine or methyldopa were excluded. After 1:1 propensity score matching, we compared cardiovascular and renal outcomes over five years. Results are reported as adjusted odds ratios (aOR) with 95% confidence intervals (CI) and as hazard ratios (HR) from Kaplan-Meier survival analysis. After matching, 11,764 patients remained in each cohort (23,528 total). Nifedipine exposure was associated with lower odds of chronic hypertension (CH, aOR 0.835, 95% CI [0.778, 0.896], p < 0.001), heart failure (HF, aOR 0.699, 95% CI [0.527, 0.926], p = 0.012), HF with reduced ejection fraction (HFrEF, aOR 0.608, 95% CI [0.418, 0.886], p = 0.009), and chronic kidney disease (CKD, aOR 0.653, 95% CI [0.492, 0.867], p = 0.003) compared to labetalol. Time-to-event analysis confirmed these findings. Among HDP patients, nifedipine exposure during the index pregnancy was associated with lower five-year risks of CH, HF, HFrEF, and CKD compared with labetalol. These findings suggest that antihypertensive choice in pregnancy may differentially affect long-term maternal cardiovascular health. • This was a large PSM HDP cohort study over 5 years from 66 healthcare organizations • Nifedipine was associated with lower chronic hypertension risk than labetalol • Nifedipine was linked to lower heart failure and HFrEF rates vs labetalol • Nifedipine was associated with lower chronic kidney disease risk vs labetalol • Kaplan-Meier survival analysis confirmed findings with significant hazard ratios