Sildenafil Prolongs Pregnancy in Women With Preeclampsia

Jim Kling

July 11, 2016

In women with preeclampsia, treatment with sildenafil citrate prolonged pregnancy by an average of 4 days compared with placebo, according to an article published online July 7 in Obstetrics & Gynecology.

"Our results also showed that sildenafil citrate administration reduces resistance to blood flow in the uteroplacental and fetoplacental circulations and is associated with a decrease in maternal mean blood pressure and that these changes are not associated with concomitant changes in the resistance to blood flow in fetal cerebral vessels," write Alberto Trapani Jr, MD, PhD, from Divisão de Tocoginecologia, Trindade Campus Universitario Florianopolis, Santa Catarina, Brazil, and colleagues.

"Reduction in maternal [mean arterial pressure], without compromising uterine artery blood flow, provides reassurance that sildenafil may be useful as an antihypertensive drug in the context of placental vascular insufficiency."

The researchers recruited 100 pregnant women with singleton pregnancies and preeclampsia and randomly assigned them to either 50 mg oral sildenafil citrate every 8 hours or placebo. In addition to the study drugs, patients received α-methyldopa (500 - 1500 mg/day) with an additional β-blocker agent (10 - 30 mg pindolol per day) as necessary, as well as intravenous hydralazine (5 - 30 mg). Two doses of betamethasone were used for patients with anticipated delivery within 72 hours.

Mean gestational age was 29.1 weeks in the sildenafil group and 30.2 weeks in the placebo group at baseline.

On average, women in the treatment group had a longer pregnancy by 4 days after randomization compared with women in the placebo group (mean, 14.4 days [95% confidence interval (CI), 12.5 - 16.6 days] compared with 10.4 days [95% CI, 8.4 - 12.3 days]; P = .008).

Secondary outcomes also favored the treatment group, including higher percentage reduction in pulsatility indices of uterine and umbilical arteries (22.5% and 18.5% compared with placebo [2.1% and 2.5%, respectively]; P < .001) and greater reduction in maternal blood pressure in the first 24 hours after randomization, which was significant with sildenafil (116.4 ± 5.1 mm Hg compared with 100.3 ± 5.6 mm Hg; P < .05) but not placebo (110.6 ± 6.2 mm Hg compared with 114.7 ± 6.5 mm Hg; P = .21).

In addition, participants in the placebo group more frequently required an additional antihypertensive drug or an increase in the dose of α-methyldopa (58% vs 32%; P < .001).

The researchers found no differences between the two groups in perinatal morbidity, mortality, or adverse effects. Some estimates indicate that each additional day of pregnancy between 24 and 32 weeks grants about a 1% increase of infant survival, but the current study was underpowered to detect such differences.

To confirm a benefit to the fetus, "studies with a larger number of patients and an earlier start of medication are required," the authors write.

A previous study showed that treatment with sildenafil reduced maternal blood pressure, but had no effect on length of pregnancy. The authors speculate that the differing results might be explained by the fact that the earlier study had a smaller number of cases, began treatment later in pregnancy (average, 31.4 vs 29.1 weeks), and used a lower dose (20 vs 50 mg).

The study was funded by the Federal University of Santa Catarina. The authors have disclosed no relevant financial relationships.

Obstet Gynecol. 2016;128:253-259. Abstract

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