Pregnant women with preeclampsia who received sildenafil citrate had a small but significant increase in duration of pregnancy compared to women who received placebo in a randomized clinical study of 100 patients.
The increase on average was 4 days (14.4 days from the start of treatment, 95% CI 12.5-16.6 vs 10.4 days, 95% CI 8.4-12.3, P = 0.008), reported Alberto Trapani, Jr., MD, of the Federal University of Santa Catarina in Brazil, and his colleagues in Obstetrics and Gynecology.
The authors said that one factor in the development of preeclampsia may be a failure of nitric oxide, a “potent vasodilator,” which helps maintain low vascular resistance in the uterus. Inhibitors of phosphodiesterase-5, such as sildenafil, increase the availability of NO.
“It is speculated that this [pregnancy] prolongation may be the result of better control of blood pressure, improved maternal and fetal blood flow, or a combination thereof,” they argued, adding that the drug had previously shown ” Promising results “in Vitro and in animal studies.
Sildenafil in the trial also performed well in the secondary outcomes. A significantly higher proportion of patients in the drug group experienced reductions in pulsatility rates (or Doppler measurements of systolic and diastolic velocities) in the uterine and umbilical arteries compared to the placebo group (22.5% versus 2, 1% and 18.5% vs. 2.5%, respectively, P
Patients receiving sildenafil also experienced significantly lower mean blood pressure 24 hours after drug administration compared to baseline (103 ± 5.6 mm Hg versus 116.4 ± 5.1 mm Hg, P
“Reduction of [mean arterial pressure] without compromising blood flow to the uterine artery provides the assurance that sildenafil may be useful as an antihypertensive drug in the context of placental vascular insufficiency,” the authors write.
Women with single pregnancies from 24 to 33 weeks of gestation with preeclampsia were randomized to 50 mg of oral sildenafil citrate or placebo every 8 hours. Demographic characteristics were similar in both groups. Most of these patients also received α-methyl-dopa, an antihypertensive drug and a beta-blocker to prevent cardiac arrhythmia.
However, a significantly larger portion of the placebo group required an additional antihypertensive agent or an increased dose of α-methyl dopa than in the sildenafil group (58% vs 32%, P <0.001).
Three patients stopped taking the medication due to headache (one in the sildenafil group and two in the control group). There were no significant differences in adverse events or neonatal outcomes between the two groups. The majority of patients in both groups were delivered by cesarean section (84% in the sildenafil group versus 88% in the control group) and most received prenatal steroids before delivery (84% versus 80%, respectively).
Trapani and colleagues said that based on the mechanism of action on the endothelium, sildenafil can be compared to other preeclampsia treatments, such as soluble FMS type tyrosine apheresis, where this antiangiogenic factor is removed from the blood of a patient. Statins and the hormone relaxin.
“The benefit of sildenafil therapy would probably be in cost, access and circumventing the counterproductive risks of nitric oxide donors, which … led to vasoconstriction rather than vasodilation,” they wrote.