1A-06 - Evaluation of the safety of continuing vs. discontinuing pre-pregnancy chronic hypertension pharmacotherapy in pregnancy: a target trial emulation approach

Background: Chronic hypertension complicates 1-5% of US pregnancies and is a leading cause of maternal morbidity and mortality.

Objectives: To evaluate the safety of continuing vs discontinuing pre-pregnancy antihypertensive treatment among pregnant individuals with chronic hypertension by emulating a target trial.

Methods: We used California Medicaid claims from 2016-2020, linked to the California Study of Mothers and Infants (SOMI). We identified patients with a pre-pregnancy chronic hypertension diagnosis code and receipt of antihypertensive treatment within a year before LMP. We applied the same criteria as the 2022 Chronic Hypertension and Pregnancy (CHAP) trial, excluding blood pressure measurements. We defined treatment as whether the patient continued or discontinued their medication before 23 weeks of gestation. The composite outcome was severe pre-eclampsia, pre-term birth (PTB), placental abruption, and/or fetal death. We used clone censor weighting. We compared analyses using weighted Kaplan-Meier (KM) and restricted mean survival time (RMST) differences to a naïve analysis that did not account for immortal time bias.

Results: The analysis included 1,063 singleton pregnancies, with 710 (61%) discontinuing antihypertensives by 23 weeks. Discontinuation was highest for beta blockers other than labetalol (57%) and lower for methyldopa (42%), labetalol (43%), and nifedipine (40%). Maternal age, body mass index, and adequacy of prenatal care were similar across groups, but those with pre-existing diabetes were less likely to discontinue (54% vs. 62%). The composite outcome occurred in 21% of the discontinuation group and 15% of the continuation group. Naïve analyses showed a protective affect against the outcome among those who continued (Risk Ratio [RR]: 0.77, 95% CI: .59-1.00; aRR: 0.75, 95% CI: 0.57-0.98). KM and RMST estimates also indicated differences (difference in weighted KM survival at 41 weeks: 11%; RMST difference: 2.14 days).

Conclusions: There was a significant reduction in risk of a composite adverse pregnancy outcome between patients who continued versus discontinued antihypertensive treatment during pregnancy. These findings are in alignment with the CHAP trial findings of decreased risk of the outcome among those who continued anti-hypertensive medication and had a chronic hypertension diagnosis prior to pregnancy. Future studies with access to blood pressure readings and relevant lab values could address potential uncontrolled confounding by indication in the present study.