318: Endothelial function is unaltered by prophylactic nitric oxide donor in women at high-risk for preeclampsia

Abstract

To study the effect of low dose prophylactic isosorbide mononitrate (ISMN) 20mg/d on the endothelial function in high-risk women receiving standard aspirin prophylaxis Design: As part of a randomized double blind placebo-controlled parallel arm superiority trial. Setting: Antenatal clinic of a tertiary teaching hospital, south India Participants and methods: One hundred women fulfilling NICE guideline criteria for aspirin prophylaxis were recruited at 12 - 16 weeks and randomised to receive either 20mg/d of ISMN or placebo, in addition to 75mg/d of oral aspirin from recruitment till delivery. Outcome measure: Changes in indices of endothelial function Sample Size (for the primary outcome): One hundred women (50 in each arm) to detect a decrease of hypertensive disorders from 20% in the placebo group to 5% in the ISMN group with a power of 80% and α at 0.05 The groups were comparable in terms of age, BMI, parity, and risk factor for preeclampsia. The vascular indices of endothelial function were recorded at recruitment and again at 24 weeks. These included flow-mediated vasodilatation index (FMVD-i), brachial-ankle pulse wave velocity, ankle-brachial index, brachial arterial stiffness index, and ankle arterial stiffness index. (Table 1). There was no significant improvement in these indices following ISMN intake. The FMVD-i actually showed a decrease following ISMN treatment. Concomitantly, there was a reduction in mean arterial pressure. The composite rate of hypertensive disorders (gestational hypertension, preeclampsia, or superimposed preeclampsia) was not significantly different between the groups (14/50, 28% in ISMN vs. 12/50, 24% in placebo group; p = 0.7). Addition of nitric oxide donor, ISMN, does not improve the endothelial function in high risk women who are on low-dose aspirin. However, it results in a slight lowering of mean arterial pressure without a concomitant reduction in the clinical event rate of hypertensive disorders.