Oral combined hydrochlorothiazide/lisinopril versus nifedipine for postpartum hypertension: a comparative-effectiveness pilot randomized controlled trial

Abstract

Angiotensin-converting enzyme inhibitors and diuretics may be underutilized for postpartum hypertension (HTN). In this pilot randomized trial, we evaluated whether oral combined hydrochlorothiazide/lisinopril (HCTZ/lisinopril) produces superior short-term blood pressure (BP) control compared to nifedipine among postpartum individuals with HTN requiring pharmacologic treatment. Individuals with chronic HTN (CHTN) or hypertensive disorder of pregnancy (HDP) with two measurements of systolic BP (SBP) ≥150 and/or diastolic BP (DBP)≥ 100 within 72 hours after delivery were randomized to either HCTZ/lisinopril or nifedipine after stratifying by diagnosis (CHTN vs HDP). The primary outcome was stage 2 HTN (SBP≥140 and/or DBP ≥90) using a home BP monitor on days 7-10 after delivery or readmission to the hospital for BP control. A pilot trial with 70 individuals was planned, given limited previous data on HCTZ/lisinopril use in postpartum care. We calculated relative risk (RR) and 95% confidence intervals (CI) in an intention-to-treat analysis and conducted a preplanned Bayesian analysis to estimate the probability of benefit or harm with a neutral informative prior. ClinicalTrials.gov: NCT05049616 Of 111 eligible individuals (10/2021 to 06/2022), 70 (63%) agreed and were randomized, with no significant differences at baseline between groups (Table 1). The primary outcome was unavailable for 12 (17%) participants. The primary outcome occurred in 27% in the HCTZ/lisinopril group compared to 43% in the nifedipine group (posterior adjusted RR, 0.74, 95% credible interval, 0.40-1.31) (Table 2). Bayesian analysis indicated an 85% posterior probability of reduced primary outcome with HCTZ/lisinopril relative to nifedipine. No differences were noted in secondary outcomes or medication adverse events. In this pilot study, our results suggest a high probability that HCTZ/lisinopril produces superior short-term BP control compared to nifedipine. These findings should be confirmed in a larger trial.View Large Image Figure ViewerDownload Hi-res image Download (PPT)