Elsevier

Journal of Clinical Lipidology

Volume 10, Issue 5, September–October 2016, Pages 1081-1090
Journal of Clinical Lipidology

Review Article
The risks of statin use in pregnancy: A systematic review

https://doi.org/10.1016/j.jacl.2016.07.002Get rights and content

Abstract

Statins are contraindicated in pregnancy; however, as women delay pregnancy and statin use increases the risk of statin exposure in pregnancy is likely to rise. In contrast to some early reports that statins are teratogenic, more recent observational studies have called into question the teratogenic risk of statins. Therefore, whether statins are associated with congenital anomalies or other pregnancy complications remains an important clinical question. This article provides an up-to-date systematic review on the risks of statins in pregnancy. We conducted a literature search to identify relevant English language studies related to statin exposure and pregnancy. Single case reports, animal studies, studies only published in abstract form, and non-English language studies were excluded. A total of 16 clinical studies were included in this systematic review. Although early uncontrolled case series reported congenital anomalies associated with statin use, more recent observational studies did not report an increased risk of congenital anomalies with statin exposure in pregnancy when compared to control groups or the prevalence of congenital anomalies in the general population. Our findings show no clear relationship of congenital anomalies with statin use in pregnancy, and our study supports the findings that statins are probably not teratogenic. However, until more information is available, statins should still be avoided in pregnancy.

Introduction

Currently, statins are contraindicated in pregnancy and were previously assigned as pregnancy category X by the Federal Drug Administration (FDA) because it was felt that the risk of the drug in pregnant women clearly outweighed any potential benefit.1 This assignment was based on animal studies that date back to the introduction of lovastatin into the market in 1987; however, the statin dose used in these animal studies was much higher than doses commonly used in clinical practice.2, 3 Because of the FDA and other national guideline4, 5 warnings about the risks of statins in pregnancy, statin use in pregnancy is uncommon. What information is available on the risks of statins in pregnancy comes from case reports, patient registries, and small cohort studies. The findings from these studies have been inconsistent, and more recent studies have found no clear link between congenital anomalies and statin exposure in pregnancy.

In light of their clinical benefits, statins are now being used more commonly in clinical practice. Statins are also being used in younger individuals who are at increased cardiovascular risk, especially in those with familial hypercholesterolemia. As more women commonly delay pregnancy into their 30s and because half of pregnancies are unplanned, the risk of statin exposure during pregnancy is increasing.6 In addition, early clinical trials are now evaluating pravastatin in pregnant women for its possible role in preventing preeclampsia.7 Therefore, whether statins are associated with congenital anomalies or other pregnancy complications remains an important clinical question. The purpose of this study was to perform a systematic review of human studies of statin exposure in pregnancy.

Section snippets

Methods

For this systematic review, we identified relevant studies by searching the following databases: Ovid MEDLINE (from 1946 to October 2014), Ovid MEDLINE In-Process, and other nonindexed citations (up to November 2014); and Ovid EMBASE Classic plus EMBASE (from1946 to November 2014). Appendix 1 includes search strategies detailing the controlled vocabulary terms, keywords, and special features, such as limits, explode, focus, and so forth that were used within each database. Our search identified

Results

A total of 16 studies were included in this systematic review. There were 5 case series, 3 cohort studies, 3 registry-based studies, 1 randomized controlled trial (Table 1), and 4 systematic reviews.

Cohort studies

Taguchi et al.13 performed a prospective, observational cohort study. They identified 64 pregnant women who had been exposed to a statin during the first trimester of their pregnancy and compared them to a matched control group of pregnant women without a known exposure to any teratogen. There was no difference in the rate of congenital anomalies, abortions or stillbirths between the statin and comparison group; however, gestational age and birth weight were lower in the statin group. Of note,

Discussion

Our updated systematic review includes 16 human studies and today is the largest systematic review on this topic. We included only human studies in our systematic review because this is most relevant to practicing clinicians. Our findings show no clear relationship with statin use in pregnancy and congenital anomalies, and our study supports the findings that statins are probably not teratogenic.

The early case series we reviewed provided mixed results. Some studies suggested that statins were

Conclusions

Although, the currently available information does not suggest that statins are major teratogens, we believe the quality of the information to date is not conclusive that statins are safe in pregnancy. In our opinion until better evidence is forthcoming statins should not be used in early pregnancy when major teratogenic risk is highest. If a woman who is taking a statin becomes pregnant, the statin should be discontinued. Reassuringly there is no quality evidence to support terminating the

Acknowledgment

Author contributions: Each author participated in the research and preparation of this article and all authors approved the final manuscript.

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