Pravastatin Versus Placebo in Pregnancies at High Risk of Term Preeclampsia

TY - JOUR

T1 - Pravastatin Versus Placebo in Pregnancies at High Risk of Term Preeclampsia

AU - Döbert, Moritz

AU - Varouxaki, Anna Nektaria

AU - Mu, An Chi

AU - Syngelaki, Argyro

AU - Ciobanu, Anca

AU - Akolekar, Ranjit

AU - De Paco Matallana, Catalina

AU - Cicero, Simona

AU - Greco, Elena

AU - Singh, Mandeep

AU - Janga, Deepa

AU - Del Mar Gil, Maria

AU - Jani, Jacques C

AU - Bartha, José Luis

AU - Maclagan, Kate

AU - Wright, David

AU - Nicolaides, Kypros H

PY - 2021/8/31

Y1 - 2021/8/31

N2 - 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.

AB - 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.

KW - Adult

KW - Biomarkers

KW - Comorbidity

KW - Female

KW - Gestational Age

KW - Humans

KW - Incidence

KW - Kaplan-Meier Estimate

KW - Mass Screening

KW - Medication Adherence

KW - Placebos/administration & dosage

KW - Pravastatin/administration & dosage

KW - Pre-Eclampsia/diagnosis

KW - Pregnancy

KW - Pregnancy Outcome

KW - Prognosis

KW - Risk Assessment

KW - Risk Factors

KW - Treatment Outcome

KW - Young Adult

U2 - 10.1161/CIRCULATIONAHA.121.053963

DO - 10.1161/CIRCULATIONAHA.121.053963

M3 - SCORING: Journal article

C2 - 34162218

VL - 144

SP - 670

EP - 679

JO - CIRCULATION

JF - CIRCULATION

SN - 0009-7322

IS - 9

ER -