Moritz Döbert1, Anna Nektaria Varouxaki1, An Chi Mu1, Argyro Syngelaki1, Anca Ciobanu1, Ranjit Akolekar2, Catalina De Paco Matallana3, Simona Cicero4, Elena Greco5, Mandeep Singh6, Deepa Janga7, Maria Del Mar Gil8,9, Jacques C Jani10, José Luis Bartha11, Kate Maclagan12, David Wright13, Kypros H Nicolaides1. 1. Fetal Medicine Research Institute, King's College Hospital, London, UK (M.D., A.N.V., A.C.M., A.S., A.C., K.H.N.). 2. Medway Maritime Hospital, Gillingham, UK (R.A.). 3. Hospital Clínico Universitario Virgen de la Arrixaca and Institute for Biomedical Research of Murcia, IMIB-Arrixaca, Spain (C.D.P.M.). 4. Homerton University Hospital, London, UK (S.C.). 5. Royal London Hospital, UK (E.G.). 6. Southend University Hospital, Westcliff-on-Sea, UK (M.S.). 7. North Middlesex University Hospital, London, UK (D.J.). 8. School of Health Sciences, Universidad Francisco de Vitoria, Madrid, Spain (M.d.M.G.). 9. Hospital Universitario de Torrejón, Madrid, Spain (M.d.M.G.). 10. University Hospital Brugmann, Université Libre de Bruxelles, Brussels, Belgium (J.C.J.). 11. Hospital Universitario La Paz, Madrid, Spain (J.L.B.). 12. Fetal Medicine Foundation, London, UK (K.M.). 13. University of Exeter, UK (D.W.).
Abstract
BACKGROUND: Effective screening for term preeclampsia is provided by a combination of maternal factors with measurements of mean arterial pressure, serum placental growth factor, and serum soluble fms-like tyrosine kinase-1 at 35 to 37 weeks of gestation, with a detection rate of ≈75% at a screen-positive rate of 10%. However, there is no known intervention to reduce the incidence of the disease. METHODS: In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1120 women with singleton pregnancies at high risk of term preeclampsia to receive pravastatin at a dose of 20 mg/d or placebo from 35 to 37 weeks of gestation until delivery or 41 weeks. The primary outcome was delivery with preeclampsia at any time after randomization. The analysis was performed according to intention to treat. RESULTS: A total of 29 women withdrew consent during the trial. Preeclampsia occurred in 14.6% (80 of 548) of participants in the pravastatin group and in 13.6% (74 of 543) in the placebo group. Allowing for the effect of risk at the time of screening and participating center, the mixed-effects Cox regression showed no evidence of an effect of pravastatin (hazard ratio for statin/placebo, 1.08 [95% CI, 0.78-1.49]; P=0.65). There was no evidence of interaction between the effect of pravastatin, estimated risk of preeclampsia, pregnancy history, adherence, and aspirin treatment. There was no significant between-group difference in the incidence of any secondary outcomes, including gestational hypertension, stillbirth, abruption, delivery of small for gestational age neonates, neonatal death, or neonatal morbidity. There was no significant between-group difference in the treatment effects on serum placental growth factor and soluble fms-like tyrosine kinase-1 concentrations 1 and 3 weeks after randomization. Adherence was good, with reported intake of ≥80% of the required number of tablets in 89% of participants. There were no significant between-group differences in neonatal adverse outcomes or other adverse events. CONCLUSIONS: Pravastatin in women at high risk of term preeclampsia did not reduce the incidence of delivery with preeclampsia. Registration: URL: https://www.isrctn.com; Unique identifier ISRCTN16123934.
BACKGROUND: Effective screening for term preeclampsia is provided by a combination of maternal factors with measurements of mean arterial pressure, serum placental growth factor, and serum soluble fms-like tyrosine kinase-1 at 35 to 37 weeks of gestation, with a detection rate of ≈75% at a screen-positive rate of 10%. However, there is no known intervention to reduce the incidence of the disease. METHODS: In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1120 women with singleton pregnancies at high risk of term preeclampsia to receive pravastatin at a dose of 20 mg/d or placebo from 35 to 37 weeks of gestation until delivery or 41 weeks. The primary outcome was delivery with preeclampsia at any time after randomization. The analysis was performed according to intention to treat. RESULTS: A total of 29 women withdrew consent during the trial. Preeclampsia occurred in 14.6% (80 of 548) of participants in the pravastatin group and in 13.6% (74 of 543) in the placebo group. Allowing for the effect of risk at the time of screening and participating center, the mixed-effects Cox regression showed no evidence of an effect of pravastatin (hazard ratio for statin/placebo, 1.08 [95% CI, 0.78-1.49]; P=0.65). There was no evidence of interaction between the effect of pravastatin, estimated risk of preeclampsia, pregnancy history, adherence, and aspirin treatment. There was no significant between-group difference in the incidence of any secondary outcomes, including gestational hypertension, stillbirth, abruption, delivery of small for gestational age neonates, neonatal death, or neonatal morbidity. There was no significant between-group difference in the treatment effects on serum placental growth factor and soluble fms-like tyrosine kinase-1 concentrations 1 and 3 weeks after randomization. Adherence was good, with reported intake of ≥80% of the required number of tablets in 89% of participants. There were no significant between-group differences in neonatal adverse outcomes or other adverse events. CONCLUSIONS: Pravastatin in women at high risk of term preeclampsia did not reduce the incidence of delivery with preeclampsia. Registration: URL: https://www.isrctn.com; Unique identifier ISRCTN16123934.
Authors: Maciej Banach; Paweł Burchardt; Krzysztof Chlebus; Piotr Dobrowolski; Dariusz Dudek; Krzysztof Dyrbuś; Mariusz Gąsior; Piotr Jankowski; Jacek Jóźwiak; Longina Kłosiewicz-Latoszek; Irina Kowalska; Maciej Małecki; Aleksander Prejbisz; Michał Rakowski; Jacek Rysz; Bogdan Solnica; Dariusz Sitkiewicz; Grażyna Sygitowicz; Grażyna Sypniewska; Tomasz Tomasik; Adam Windak; Dorota Zozulińska-Ziółkiewicz; Barbara Cybulska Journal: Arch Med Sci Date: 2021-11-08 Impact factor: 3.318
Authors: Jelani K Grant; Sarah Snow; Michelle Kelsey; Jennifer Rymer; Anna E Schaffer; Manesh R Patel; Robert W McGarrah; Neha J Pagidipati; Nishant P Shah Journal: Curr Cardiol Rep Date: 2022-07-29 Impact factor: 3.955
Authors: Jyoti Sharma; Jan McAlister; Niti R Aggarwal; Janet Wei; Puja K Mehta; Odayme Quesada; Deirdre Mattina; Nandita S Scott; Erin D Michos; Zainab Mahmoud; Karla Kurrelmeyer; Glaucia Maria Moraes De Oliveira; Kathryn J Lindley Journal: Am J Prev Cardiol Date: 2022-03-13
Authors: Kaspar Ratnik; Kristiina Rull; Oliver Aasmets; Triin Kikas; Ele Hanson; Kalle Kisand; Krista Fischer; Maris Laan Journal: Front Cardiovasc Med Date: 2022-07-27
Authors: Anca Maria Panaitescu; Mihaela Roxana Popescu; Anca Marina Ciobanu; Nicolae Gica; Brindusa Ana Cimpoca-Raptis Journal: Medicina (Kaunas) Date: 2021-12-01 Impact factor: 2.430