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

• Published in: Expert opinion on drug safety Vol. 23; no. 3; p. 313
• Main Authors: Wu, Tingxi, Shi, Yanfeng, Zhu, Bin, Li, Dandan, Li, Zhe, Zhao, Zhigang, Zhang, Yang
• Format: Journal Article
• Language: English
• Published: England 03.03.2024
• Subjects: Adverse Drug Reaction Reporting Systems; Bayes Theorem; Female; Fenofibrate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Infant, Newborn; Lovastatin; Pharmacovigilance; Pravastatin; Pregnancy; Premature Birth - epidemiology; Stillbirth - epidemiology; United States - epidemiology; United States Food and Drug Administration; United States; Pregnancy; FAERS; disproportionality analysis; statins; evolocumab; fenofibrate; Bayesian analysis
• ISSN: 1744-764X
• DOI: 10.1080/14740338.2023.2251888

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. 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). 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; IC  = 0.63), and pravastatin demonstrated increased risks of preterm birth (ROR = 4.89, 95% CI, 3.65-6.54; IC  = 1.69) and low birth weight (ROR = 9.60, 95% CI, 5.56-16.56; IC  = 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. 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.