Pravastatin suppresses inflammatory cytokines and endothelial activation in patients at risk of developing preeclampsia: INOVASIA study

Akbar, Muhammad Ilham Aldika; Yosediputra, Angelina; Pratama, Raditya Ery; Fadhilah, Nur Lailatul; Sulistyowati, Sulistyowati; Amani, Fariska Zata; Dachlan, Erry Gumilar; Angsar, Muhammad Dikman; Dekker, Gustaaf A.

doi:10.1080/14767058.2021.1879785

Cited by 9 publications

(22 citation statements)

References 39 publications

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“…The other important pre-specified outcome was the beneficial effect of 40 mg of pravastatin on various serum markers. We recently published on the beneficial effects of pravastatin on various inflammatory cytokines and endothelin levels [28]. The current paper shows that administration of pravastatin started before 20 weeks more or less stabilizes sFlt-1 and PlGF levels, the sFlt-1/PlGF ratio, and sEng levels.…”

Section: Discussionmentioning

confidence: 64%

“…This report, on the Surabaya arm of the INOVASIA study, is the first randomized study on the use of prophylactic pravastatin with preeclampsia as primary outcome. The reason for this initial report on the Surabaya arm within this multicenter trial relates to the fact that the Surabaya center was the only center with the capacity to look at various biomarkers and levels of angiogenic and anti-angiogenic factors [28].…”

Section: Discussionmentioning

confidence: 99%

“…Statins have pleiotropic effects which may, in theory, be beneficial in preventing preeclampsia including: immunomodulatory and anti-inflammatory effects, and reduction in free oxygen radical formation and smooth muscle cell proliferation [4]. We recently demonstrated that pravastatin reduces levels of pro-inflammatory cytokines and endothelial activation markers in patients at risk of developing preeclampsia [28].…”

Section: Introductionmentioning

confidence: 99%

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INOVASIA Study: A Randomized Open Controlled Trial to Evaluate Prophylactic Pravastatin in the Prevention of Preeclampsia and its Effects on sFlt1/PLGF Levels in Pregnant Women at High Risk of Developing Preeclampsia

Akbar

Yosediputra

Re³

et al. 2021

Preprint

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Objectives The study aim is to evaluate the effect of pravastatin to prevent preeclampsia (PE) in pregnant women at a high risk of developing preeclampsia and the maternal and perinatal outcomes and the sFlt1/PLGF ratio in the Surabaya cohort of the INOVASIA trial. Setting This study involved 2 academic hospital (a tertiary and secondary center) in Surabaya, Indonesia. Participants 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 10-20 weeks gestational age. Inteventions 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 14-20 weeks gestation until delivery. Research blood samples were collected before the first dose of pravastatin, and just before delivery. Primary and Secondary Outcomes The primary outcome was the rate of maternal preeclampsia, secondary outcomes included maternal-perinatal outcomes and sFlt-1, PLGF, sFlt-1/PlGF ratio and sEng levels. Results The rate of preeclampsia was (non-significantly) lower in the pravastatin group compared with the control group (17.5% vs 35%). The pravastatin group also had a (non-significant) lower rate of severe preeclampsia, HELLP syndrome, acute kidney injury and severe hypertension. The rate of (iatrogenic) preterm delivery was significantly lower (p 0.048) in the pravastatin group (n=4) compared with the controls (n=12). Neonates in the pravastatin group had significantly higher birthweights, higher Apgar scores, and lower composite neonatal morbidity and NICU admission rates. All biomarkers show a significant deterioration in the control group compared with non-significant changes in the pravastatin group. Conclusions Pravastatin holds promise in the secondary prevention of preeclampsia and placenta-mediated adverse perinatal outcomes by improving the anti-angiogenic/pro-angiogenic imbalance. Trial Registration Clinical Trial Gov (ID: NCT03648970)

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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INOVASIA Study: A Randomized Open Controlled Trial to Evaluate Prophylactic Pravastatin in the Prevention of Preeclampsia and its Effects on sFlt1/PLGF Levels in Pregnant Women at High Risk of Developing Preeclampsia

Akbar

Yosediputra

Re³

et al. 2021

Preprint

Self Cite

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show abstract

“…Statins have pleiotropic effects which may, in theory, be beneficial in preventing preeclampsia including: immunomodulatory and anti-inflammatory effects, and reduction in free oxygen radical formation and smooth muscle cell proliferation (24). We recently demonstrated that pravastatin reduces levels of pro-inflammatory cytokines and endothelial activation markers in patients at risk of developing preeclampsia (28).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…The reason for this initial report on the Surabaya arm within this multicenter trial relates to the fact that the Surabaya centers were the first to start the study, while the other centers faced massive delays partly due to the COVID pandemic. The Surabaya center were also the only centers with the capacity to look at various biomarkers and levels of angiogenic and anti-angiogenic factors (28).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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

Akbar

Yosediputra

Pratama³

et al. 2021

Am J Perinatol

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Objectives To evaluate the effect of pravastatin to prevent preeclampsia (PE) in pregnant women at a high risk of developing preeclampsia and the maternal and perinatal outcomes and the sFlt1/PLGF ratio. Study Design This is an open labelled RCT part of INOVASIA 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 10-20 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 14-20 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 preeclampsia, maternal-perinatal outcomes, and sFlt-1, PLGF, sFlt-1/PlGF ratio and sEng levels. Results The rate of preeclampsia was (non-significantly) lower in the pravastatin group compared with the control group (17.5% vs 35%). The pravastatin group also had a (non-significant) lower rate of severe preeclampsia, HELLP 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 birthweights (2931 + 537 vs 2625 + 872 g; p=0.006), lower Apgar 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 non significant changes in the pravastatin group. Conclusions Pravastatin holds promise in the secondary prevention of preeclampsia and placenta-mediated adverse perinatal outcomes by improving the angiogenic imbalance.

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INOVASIA Study: A Multicenter Randomized Clinical Trial of Pravastatin to Prevent Preeclampsia in High-Risk Patients

et al. 2022

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Objective To determine if treatment with pravastatin prevents preeclampsia in pregnant patients at risk for preeclampsia. Material & Methods The study was performed in four major tertiary hospitals in Surabaya, Bandung, and Makassar between 2017-2021. Pregnant women at high risk of developing preeclampsia were recruited and randomized into an intervention group and control group. The control group received low dose aspirin (80 mg) and calcium (1 g) daily, while the intervention group received additional pravastatin (20 mg twice daily) started from 14-20 weeks’ gestation until delivery. The pregnancy was followed until delivery, and the clinical data was collected. The primary outcome was the occurrence of preeclampsia. Result A total of 173 people participated in this study, including 86 in the control group and 87 in the pravastatin group. The pravastatin group had a significantly lower rate of preterm preeclampsia (13.8% vs 26.7%; p=0.034; (OR=0.034, 95% CI: 0.202-0.905) and preterm birth (16.1 % vs. 36 %; p=0.003; OR= 0.340, 95% CI: 0.165-0.7), mostly indicated preterm birth. Preeclampsia occurs later in the pravastatin group than in the control group (36.39+2.32 vs 34.89+3.38 weeks, p=0.048). Overall the pravastatin group had better perinatal outcomes. Neonates with low Apgar scores (<7) at 1 minute (5.7% vs 25.6%, p=0.000) and 5 minutes (2.3% vs 25.6%, p=0.028) were significantly less common in the pravastatin group. Additionally, the rate of low birthweight babies (< 2500g) was lower in pravastatin group (27.6% vs 40.7%; p= 0.069). Conclusion Pravastatin (20 mg bid) significantly reduces the risk for preterm preeclampsia and preterm birth in women at a high risk of developing preeclampsia.

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Pravastatin suppresses inflammatory cytokines and endothelial activation in patients at risk of developing preeclampsia: INOVASIA study

Cited by 9 publications

References 39 publications

INOVASIA Study: A Randomized Open Controlled Trial to Evaluate Prophylactic Pravastatin in the Prevention of Preeclampsia and its Effects on sFlt1/PLGF Levels in Pregnant Women at High Risk of Developing Preeclampsia

INOVASIA Study: A Randomized Open Controlled Trial to Evaluate Prophylactic Pravastatin in the Prevention of Preeclampsia and its Effects on sFlt1/PLGF Levels in Pregnant Women at High Risk of Developing Preeclampsia

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

INOVASIA Study: A Multicenter Randomized Clinical Trial of Pravastatin to Prevent Preeclampsia in High-Risk Patients

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