RANDOMIZED CONTROLLED TRIAL OF KETANSERIN AND ASPIRIN IN PREVENTION OF PREECLAMPSIA

Background Pre-eclampsia is associated with extensive endothelial-cell damage and platelet activation, resulting in lower production of vaso dilator prostaglandins and increased release of the vasoconstrictors t hromboxane A(2) and serotonin. Damage to endothelial-cell serotonin-1 receptors leaves vasoconstriction and; platelet aggregation mediated b y serotonin-2 receptors unopposed. We investigated the role of ketanse rin, a selective serotonin-2-receptor antagonist, in lowering the rate of pre-eclampsia among pregnant women with mild to moderate hypertens ion. Methods We recruited 138 pregnant women into a double blind, rand omised, placebo-controlled trial. They had diastolic blood pressure pe rsistently more than 80 mm Hg before 20 weeks' gestation. 69 women rec eived ketanserin and 69 received placebo. Both groups also received as pirin. Patients were initially given two tablets daily, increased to f our tablets daily in diastolic blood pressure was more than 90 mm Hg. Primary outcomes were the development of pre-eclampsia and severe hype rtension, and perinatal mortality. Findings There were significantly f ewer cases of preeclampsia (two vs 13; relative risk 0.15 [95% CI 0.04 -0.66], p=0.006) and severe hypertension (six vs 17; p=0.02) in the ke tanserin than in the placebo group. There was also a trend towards les s perinatal mortality (one vs six deaths) but this was not significant (p=0.28). Rates of abruptio placentae and pre-eclampsia before 34 wee ks' gestation were lower in the ketanserin group, and mean birthweight was significantly higher. Interpretation We found an association betw een the addition of ketanserin to aspirin and a decrease in the number of cases of preeclampsia and severe hypertension, as well as improved pregnancy outcome among patients with mild to moderate midtrimester h ypertension.