The article by Winterfeld et al. adds another piece of evidence supporting the safety of statins in pregnancy. Classification of statins as pregnancy category X by the Food and Drug Administration since the beginning of the 1980s was based mainly on case reports and has remained unquestioned primarily because there was no therapeutic indication of statin use in pregnancy. A pragmatic evaluation of statin safety in pregnancy is needed not only because of the growing likelihood of a pregnant woman receiving statin therapy (e.g. inherited hyperlipidaemia, increasing pregnancy rates for women over 35 years old), as the authors rightly note, but also because statins are important promising candidates for the prevention of adverse pregnancy outcomes in high-risk women.
There is a strong need for pharmacological agents for pre-eclampsia, because there is no effective prophylactic therapy and delivery remains the only definitive treatment. Certain pathogenetic and pathophysiological phenomena such as endothelial dysfunction and imbalanced immunological and inflammatory responses are parallel in pre-eclampsia and atherosclerosis. Statins have become established in the primary and secondary prevention of cardiovascular disease. Their pleiotropic beneficial effects, which extend far beyond lipid-lowering and involve endothelial function modification, immunoinflammatory responses and thrombus formation, offer a theoretical basis for using statins in the prevention of pre-eclampsia. Studies using animal models of pre-eclampsia have shown promising results. Low-dose aspirin, by inhibiting the production of thromboxane A2, has been shown to reduce the risk of pre-eclampsia and, moreover, a synergy between aspirin and statins in reducing cardiovascular events has been demonstrated. Hence, it is plausible that a combination of aspirin with a statin initiated early (before 16 weeks) and administered throughout the pregnancy, would have increased efficacy in the prevention of pre-eclampsia. Further therapeutic applications of statins in pregnancy could also be considered, such as the potential benefits from its use (alone or in combination with aspirin) in lowering the elevated fibrinolysis inhibitor Lipoprotein (a), which appears to be a risk factor not only for pre-eclampsia, but also other obstetric complications like miscarriages or intrauterine growth restriction.
The first pilot randomised controlled trials to assess the safety of statins in pregnancy are already underway and as soon as enough evidence is provided, a new group of therapeutic agents could be introduced into obstetric practice, opening new roads in the prevention of common pregnancy complications.
Disclosure of interest