Comparative effectiveness of initiating nifedipine versus labetalol in early gestation for chronic hypertension in pregnancy

BackgroundLimited data exist on the comparative effectiveness and safety of first-line medications to treat chronic hypertension in pregnancy. We compared nifedipine versus labetalol initiation before 23 weeks gestation for risk of pregnancy loss (miscarriage or stillbirth) and preterm birth (<37 weeks). MethodsWe identified pregnancies in Meratives MarketScan commercial claims data with estimated last menstrual periods between July 1, 2016 and February 1, 2022. We included those with a new nifedipine or labetalol fill before 23 weeks gestation. We estimated risks, risk differences (RDs) per 100 pregnancies, and risk ratios (RRs) among nifedipine versus labetalol initiators using a weighted Aalen-Johansen estimator to account for confounding and informative censoring. We also conducted a post hoc analysis to estimate the comparative effect of nifedipine versus labetalol on risk of preeclampsia. ResultsWe identified 987 nifedipine and 4,570 labetalol initiators during the study period. The weighted risk of pregnancy loss was 7.0% among nifedipine and 6.0% among labetalol initiators (RD=1.1 [-0.7, 2.8]; RR=1.18 [0.87, 1.59]). Weighted risks of preterm birth were 29.4% versus 22.2%, respectively (RD=7.2 [3.9, 10.5], RR=1.32 [1.13, 1.55]). In post hoc analyses, the weighted risks of preeclampsia were 38.6% versus 33.9%, respectively (RD=4.7 [0.7, 8.7], RR=1.14 [1.01, 1.28]). Findings were consistent across various sensitivity analyses. ConclusionsCompared to labetalol initiators, nifedipine initiators experienced an increased risk of preterm birth but not pregnancy loss. The elevated risk of preterm birth may be explained by an increased risk of preeclampsia among nifedipine initiators, resulting in medically indicated preterm birth. Clinical Perspective What is new?O_LIInitiating nifedipine, compared to labetalol, before 23 weeks gestation as a first-line antihypertensive was associated with a 7.2 percentage point increased risk of preterm live birth (95% CI: 3.9, 10.5) and 4.7 percentage point increased risk of preeclampsia (95% CI: 0.7, 8.7). C_LIO_LINifedipine and labetalol were associated with a similar risk of pregnancy loss (risk difference: 1.1 per 100 pregnancies [95% CI: -0.7, 2.8]). C_LIO_LIThese findings were robust across multiple sensitivity analyses. C_LI What are the clinical implications?O_LIInitiating labetalol, compared to nifedipine, prior to 23 weeks gestation for treatment of chronic hypertension in pregnancy may lead to lower risk of preeclampsia and preterm live birth in real-world settings. C_LIO_LIWhile high-quality data from clinical trials clearly support antihypertensive therapy for chronic hypertension in pregnancy, our findings illustrate that the first-line medications may have different comparative safety and effectiveness profiles. C_LIO_LIThese data are important for informing shared decision-making between providers and patients managing chronic hypertension in pregnancy. C_LI