Nifedipine plus sildenafil reduces preterm birth more than nifedipine alone

Reference

Maher MA, Sayyed TM, El-khadry SW. Nifedipine alone or combined with sildenafil citrate for management of threatened preterm labour: a randomised trial. BJOG 2019;126(6):729-735.

Synopsis

Sildenafil citrate has a smooth muscle relaxation effect. These investigators in Egypt conducted a single-blind randomized controlled trial comparing nifedipine plus sildenafil with nifedipine alone for the arrest of preterm labor between 24 and 34 weeks' gestation. They included 239 women with singleton pregnancies and threatened preterm labor, defined as persistence of at least 2 symptomatic contractions within 10 minutes for at least 60 minutes, plus cervical change. The authors excluded women with cervical dilation greater than 4 cm, ruptured membranes, suspected chorioamnionitis, major chronic medical disease, contraindication to either study medication, or other general contraindication to tocolytic therapy. Patients were randomly allocated to receive 20 mg oral nifedipine, followed by 10 mg nifedipine every 6 to 8 hours, plus 25 mg vaginal sildenafil intravaginally every 8 hours, or the oral nifedipine alone. Medications were continued for 48 to 72 hours, then the women were observed for an additional 24 hours to detect whether contractions recurred. Stable patients were discharged and offered prophylactic vaginal progesterone to prevent recurrent preterm labor. Nearly all women were followed up until delivery, with only approximately 5% lost (n = 13). Combined treatment was associated with a higher undelivered rate during hospitalization (82% vs 67%; P = .018; number needed to treat [NNT] 8; 95% CI 4 - 45), fewer deliveries within 7 days of admission (9% vs 20%; P = .014; NNT 9; 5 - 45), and prolonged mean days to delivery (29 vs 7; P = .002). Neonatal outcomes were correspondingly better with combined treatment, with fewer intensive care admissions (31% vs 44%; P = .043; NNT 9; 4 - 260), fewer deliveries at less than 32 weeks' gestation (21% vs 38%; P = .003; NNT 5; 3 - 10), and higher mean birthweight (1900 g vs 1500 g; P = .018). Only minor adverse events, such as headache or flushing, were observed in both study groups, with no differences between groups. The sample size was too small to assess any rare adverse events, and long-term follow-up for adverse outcomes was also lacking.