Pre-eclampsia is associated with extensive endothelial-cell damage and platelet activation, resulting in lower production of vasodilator prostaglandins and increased release of the vasoconstrictors thromboxane A₂ and serotonin. Damage to endothelial-cell serotonin-1 receptors leaves vasoconstriction and platelet aggregation mediated by serotonin-2 receptors unopposed. We investigated the role of ketanserin, a selective serotonin-2-receptor antagonist, in lowering the rate of pre-eclampsia among pregnant women with mild to moderate hypertension.

We recruited 138 pregnant women into a doubleblind, randomised, placebo-controlled trial. They had diastolic blood pressure persistently more than 80 mm Hg before 20 weeks' gestation. 69 women received ketanserin and 69 received placebo. Both groups also received aspirin. Patients were initially given two tablets daily, increased to four tablets daily in diastolic blood pressure was more than 90 mm Hg. Primary outcomes were the development of pre-eclampsia and severe hypertension, and perinatal mortality.

There were significantly fewer 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 ketanserin than in the placebo group. There was also a trend towards less perinatal mortality (one vs six deaths) but this was not significant (p=0�28). Rates of abruptio placentae and pre-eclampsia before 34 weeks' gestation were lower in the ketanserin group, and mean birthweight was significantly higher.

We found an association between the addition of ketanserin to aspirin and a decrease in the number of cases of pre-eclampsia and severe hypertension, as well as improved pregnancy outcome among patients with mild to moderate midtrimester hypertension.