Pregnancy-related adverse events associated with statins: a real-world pharmacovigilance study of the FDA Adverse Event Reporting System (FAERS)

ABSTRACTBackground Statins, previously rated as pregnancy category X agents, were contraindicated during pregnancy due to the teratogenic effects observed in animal studies. However, it is still controversial whether statins have detrimental impact on pregnant women or not, and some studies even suggest a potential benefit of statin use against pregnancy complications. The aim of this study was to explore whether maternal exposure to statins is associated with increased rates of pregnancy-related adverse events (AEs), including abortion, abortion spontaneous, preterm birth, low birth weight, stillbirth/fetal death, and fetal complications.Research design and methods Data from 1 January 2004 to 30 June 2022 were extracted through the U.S. FDA Adverse Event Reporting System (FAERS) database, to conduct disproportionality analysis and Bayesian analysis by reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) algorithms. To identify the potential risks of pregnancy-related AEs, each statin was compared to all the other drugs, all the other statins, and the reference drugs (fenofibrate and evolocumab).Results A total of 477 cases involving pregnancy-related AEs associated with stains were submitted to the FAERS database by healthcare professionals. No obvious disproportionate association of abortion, abortion spontaneous, or stillbirth/fetal death was identified for all statins during gestation. In comparison with all the other drugs, lovastatin showed an increased risk of fetal complications (ROR = 2.45, 95% CI, 1.22–4.95; IC025 = 0.63), and pravastatin demonstrated increased risks of preterm birth (ROR = 4.89, 95% CI, 3.65–6.54; IC025 = 1.69) and low birth weight (ROR = 9.60, 95% CI, 5.56–16.56; IC025 = 1.88). Similar results were found when compared lovastatin or pravastatin with fenofibrate. Furthermore, statins were associated with higher proportion of fetal complications and preterm birth when comparing with evolocumab.Conclusions Statins did not increase the risk of pregnancy-related AEs, including abortion, abortion spontaneous, or stillbirth/fetal death. However, we did find significant disproportionality signals for preterm birth and low birth weight associated with pravastatin, and lovastatin was related to a higher proportion of fetal complications. The results in this study may provide evidence on the safety of statins during pregnancy, which need to be verified in further investigations.KEYWORDS: PregnancystatinsfenofibrateevolocumabFAERSdisproportionality analysisBayesian analysis Declaration of interestsThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Data availability statementThe data are available in the FDA Adverse Event Reporting System (FAERS): https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.htmlAuthor contribution statementYang Zhang and Tingxi Wu designed the research, analyzed the data, and wrote the manuscript draft; Tingxi Wu, Yanfeng Shi, Dandan Li, and Zhe Li contributed to the data collection and analysis; Bin Zhu prepared the tables and figures; Yang Zhang and Zhigang Zhao directed the research, reviewed and edited the manuscript.Supplemental dataSupplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2023.2251888.Additional informationFundingThis paper was not funded.