Background: Discontinuing statin therapy before pregnancy remains challenging, especially in high-risk women. We evaluated the risks of maternal cardiovascular, gestational, and fetal outcomes associated with continuing versus discontinuing statin therapy before the last menstrual period (LMP).
Methods: We conducted a nationwide cohort study using data from the National Health Insurance Database of South Korea collected between 2009 and 2023. Women who used statins for 12 to 24 weeks before their LMP between 2010 and 2022 were stratified by whether they discontinued statins before their LMP. Maternal cardiovascular outcomes were major adverse cardiovascular and cerebrovascular events (MACCE), a composite of myocardial infarction, stroke, coronary revascularization, and cardiovascular death. Gestational and fetal outcomes included preterm delivery, pre-eclampsia/eclampsia, other hypertensive disorders of pregnancy, gestational diabetes, nonlive birth, major congenital malformations, and low birth weight. Propensity scores were estimated from potential confounders, and overlap weighting was applied to control for confounding factors. The weighted hazard ratio for MACCE was estimated using a Cox proportional hazards model. Weighted risk ratios for gestational outcomes were estimated using generalized linear models with 95% CIs.
Results: Among 13 374 women with preconception statin use, 7493 (56.0%) continued statin therapy beyond their LMP, and 5881 (44.0%) discontinued statin therapy before their LMP. Compared with continued statin, discontinued statin before the LMP was not associated with an increased risk of maternal MACCE (hazard ratio, 1.00 [95% CI, 0.72-1.37]). Even among women with established familial hypercholesterolemia (n=2435; hazard ratio, 0.92 [95% CI, 0.46-1.85]) or atherosclerotic cardiovascular disease (n=1879; hazard ratio, 0.83 [95% CI, 0.46-1.49]), there was no significant difference in the risk of MACCE between the 2 groups. Statin discontinuation was associated with a lower risk of nonlive birth (risk ratio, 0.89 [95% CI, 0.82-0.95]) and low birth weight (risk ratio, 0.88 [95% CI, 0.78-0.99]).
Conclusions: In this nationwide cohort, discontinuation of statins at pregnancy was not associated with increased maternal cardiovascular risk, including among high-risk women. Secondary analyses suggested differences in fetal outcomes between groups; however, these findings should be interpreted cautiously given the observational design.
Keywords: adverse birth outcomes; atherosclerotic disease; fetal death; pregnant woman; statin.