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

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

Note

This study is registered with Clinical Trial Gov. (ID: NCT03648970).

Data Availability Statement

The data of this study will be available on request for IPD analysis and systematic review.

Authors' Contributions

M.I.A.A. played a pivotal role in conceptualizing and designing the study, overseeing its implementation and execution, interpreting and analyzing the data, and drafting and revising the various versions of the manuscript. Additionally, M.I.A.A. took charge of the final version and managed the submission and communication with the journal. A.Y., R.E.P., N.L.F., S.S., F.Z.A., and E.E. were actively involved in patient selection, recruitment, and maternal-perinatal data collection. E.G.D., M.D.A., and G.D. significantly contributed to the study's conceptualization and design, as well as the drafting and revision processes, ultimately preparing the final version of the manuscript.

Publikationsverlauf

Eingereicht: 05. Oktober 2021

Angenommen: 15. Oktober 2021

Accepted Manuscript online:
19. Oktober 2021

Artikel online veröffentlicht:
20. Dezember 2021

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