3G-06 - Periconceptional Statin Discontinuation, Maternal Cardiovascular Events, and Pregnancy Outcomes: A Target Trial Emulation

Background: In 2021, the US Food and Drug Administration removed the warning against statin use during pregnancy based on observational studies showing no increased risk of major congenital malformations. However, the impact of continued statin use in pregnancy on other maternal and pregnancy outcomes remains uncertain.

Objectives: To evaluate the risks of maternal major adverse cardiovascular events (MACE: myocardial infarction, stroke, all-cause death, and revascularization), non-live birth, and low birth weight ( < 2000g) associated with no statin discontinuation before pregnancy, compared with discontinuation before pregnancy.

Methods: This nationwide cohort study utilized Korea’s National Health Insurance Service database (2009–2023). Women with a statin prescription during the 24 to 12 weeks before the last menstrual period (LMP) were included and stratified based on whether they discontinued statin treatment before the LMP. Women were followed until the date of outcome occurrence or the end of the study period; for non-live birth outcomes, follow-up was additionally censored at the end of pregnancy. Weighted hazard ratios (HR) with 95% confidence intervals (CI) for the risk of MACE and non-live birth were estimated using the Cox proportional hazards model. We estimated the wRR of low birth weight using a generalized linear model, while weighted marginal mean differences were calculated for birth weight.

Results: A total of 13,374 eligible pregnancies were identified, with 7,493 and 5,881 continuers and discontinuers, repectively. The crude and weighted HRs were 1.62 (1.24–2.12) and 1.20 (0.91–1.56), respectively, for not discontinuing statin past LMP, compared to discontinuation before LMP. The crude and weighted HRs for non-live births were 1.38 (1.27–1.48) and 1.16 (1.07–1.26), respectively. The wRR for low birth weight among those continuing statin beyond LMP was 0.11 (0.90–1.36). Continued statin use was associated with a lower birth weight compared with discontinuation before LMP (-36.8g, 95% CI -66.9g to -6.6g).

Conclusions: Continued statin use during pregnancy was not associated with risks of MACE and low birth weight but was associated with a higher risk of fetal loss. Clinicians should carefully consider associated risks when making decisions on lipid-lowering strategies during pregnancy.