INOVASIA Study: A Randomized Open Controlled Trial to Evaluate Pravastatin to Prevent Preeclampsia and Its Effects on sFlt1/PlGF Levels

Muhammad Ilham Aldika Akbar; Angelia Yosediputra; Raditya E. Pratama; Nur L. Fadhilah; Sulistyowati Sulistyowati; Fariska Z. Amani; Ernawati Ernawati; Erry G. Dachlan; Muhammad D. Angsar; Gus Dekker

doi:10.1055/a-1673-5603

American Journal of Perinatology, Table of Contents

Am J Perinatol 2024; 41(03): 300-309
DOI: 10.1055/a-1673-5603

Original Article

INOVASIA Study: A Randomized Open Controlled Trial to Evaluate Pravastatin to Prevent Preeclampsia and Its Effects on sFlt1/PlGF Levels

Muhammad Ilham Aldika Akbar

¹Department of Obstetrics and Gynecology Faculty of Medicine Universitas Airlangga, Mayjen Prof Dr. Moestopo Street No. 47, Surabaya, Indonesia

²Department of Obstetrics and Gynecology Universitas Airlangga Hospital, Mulyorejo Street, Surabaya, Indonesia

,

Angelia Yosediputra

³Department of Obstetrics and Gynecology Dr. Soetomo General Academic Hospital, Mayjen Prof Dr. Moestopo Street No. 6-8, Surabaya, Indonesia

,

Raditya E. Pratama

⁴Department of Obstetrics and Gynecology Ibnu Sina General Hospital, Dr. Wahidin Sudirohusodo Street No243B, Gresik, Indonesia

,

Nur L. Fadhilah

⁵Department of Obstetrics and Gynecology, Semen Gresik General Hospital, RA. Kartini Street No. 280, Gresik, Indonesia

,

Sulistyowati Sulistyowati

⁶Department Obstetrics and Gynecology Blambangan General Hospital, Letkol Istiqlah Street No. 49, Banyuwangi, Indonesia

,

Fariska Z. Amani

⁷Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Nadhlatul Ulama, Raya Jemursari Street No. 57, Surabaya, Indonesia

,

Ernawati Ernawati

¹Department of Obstetrics and Gynecology Faculty of Medicine Universitas Airlangga, Mayjen Prof Dr. Moestopo Street No. 47, Surabaya, Indonesia

³Department of Obstetrics and Gynecology Dr. Soetomo General Academic Hospital, Mayjen Prof Dr. Moestopo Street No. 6-8, Surabaya, Indonesia

,

Erry G. Dachlan

¹Department of Obstetrics and Gynecology Faculty of Medicine Universitas Airlangga, Mayjen Prof Dr. Moestopo Street No. 47, Surabaya, Indonesia

³Department of Obstetrics and Gynecology Dr. Soetomo General Academic Hospital, Mayjen Prof Dr. Moestopo Street No. 6-8, Surabaya, Indonesia

,

Muhammad D. Angsar

¹Department of Obstetrics and Gynecology Faculty of Medicine Universitas Airlangga, Mayjen Prof Dr. Moestopo Street No. 47, Surabaya, Indonesia

²Department of Obstetrics and Gynecology Universitas Airlangga Hospital, Mulyorejo Street, Surabaya, Indonesia

³Department of Obstetrics and Gynecology Dr. Soetomo General Academic Hospital, Mayjen Prof Dr. Moestopo Street No. 6-8, Surabaya, Indonesia

,

Gus Dekker

¹Department of Obstetrics and Gynecology Faculty of Medicine Universitas Airlangga, Mayjen Prof Dr. Moestopo Street No. 47, Surabaya, Indonesia

⁸Department of Obstetrics and Gynecology Lyell McEwin Hospital, The University of Adelaide, Adelaide, South Australia

› Author Affiliations

Abstract

Objectives This study aimed to evaluate the effect of pravastatin to prevent preeclampsia (PE) in pregnant women at a high risk of developing PE and the maternal and perinatal outcomes and the soluble fms-like tyrosine kinase 1/placental growth factor (sFlt1/PlGF) ratio.

Study Design This is an open-labeled randomized controlled trial (RCT), a part of INOVASIA (Indonesia Pravastatin to Prevent Preeclampsia study) trial. Pregnant women at a high risk of developing PE were recruited and randomized into an intervention group (40) and a control group (40). The inclusion criteria consisted of pregnant women with positive clinical risk factor and abnormal uterine artery Doppler examination at 10 to 20 weeks' gestational age. The control group received low dose aspirin (80 mg/day) and calcium (1 g/day), while the intervention group received additional pravastatin (20-mg twice daily) starting from 14 to 20 weeks' gestation until delivery. Research blood samples were collected before the first dose of pravastatin and before delivery. The main outcome was the rate of maternal PE, maternal–perinatal outcomes, and sFlt-1, PlGF, sFlt-1/PlGF ratio, and soluble endoglin (sEng) levels.

Results The rate of PE was (nonsignificantly) lower in the pravastatin group compared with the control group (17.5 vs. 35%). The pravastatin group also had a (nonsignificant) lower rate of severe PE, HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome, acute kidney injury, and severe hypertension. The rate of (iatrogenic) preterm delivery was significantly (p = 0.048) lower in the pravastatin group (n = 4) compared with the controls (n = 12). Neonates in the pravastatin group had significantly higher birth weights (2,931 ± 537 vs. 2,625 ± 872 g; p = 0.006), lower Apgar's scores < 7 (2.5 vs. 27.5%, p = 0.002), composite neonatal morbidity (0 vs. 20%, p = 0.005), and NICU admission rates (0 vs. 15%, p = 0.026). All biomarkers show a significant deterioration in the control group compared with nonsignificant changes in the pravastatin group.

Conclusion Pravastatin holds promise in the secondary prevention of PE and placenta-mediated adverse perinatal outcomes by improving the angiogenic imbalance.

Key Points

Prophylactic pravastatin was associated with a significantly lower rate of adverse perinatal outcome.
The sFlt1/PlGF ratio stabilized in the pravastatin group compared with a deterioration in the control group.
Pravastatin holds promise in the secondary prevention of PE and placenta-mediated adverse perinatal outcomes.

Keywords

preeclampsia - prevention - pravastatin - maternal health - perinatal morbidity

Full Text

References

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