Efficacy, safety and tolerability of bosentan as an adjuvant to sildenafil and sildenafil alone in persistant pulmonary hypertension of newborn (PPHN).

Background: Pulmonary Arterial Hypertension (PAH) carries a poor prognosis in both adult and pediatric patients. It is a life-threatening condition in newborns. Current recommendations advocate the use of targeted monotherapy as a first-line approach for the treatment of Persistent Pulmonary Hypertension of the Newborn (PPHN). In case of an inadequate clinical response to treatment, an addition of a second or third agent is considered. PAH is usually managed with a phosphodiesterase 5 inhibitor or an endothelin receptor blocker. There are limited pediatric studies that address questions like which class of therapy should be initiated first or if a combination should be initiated together. With this background, the present study was initiated to compare the efficacy, safety, and tolerability of bosentan as an adjuvant to sildenafil and sildenafil alone in PPHN.

Results: A total of 40 patients were enrolled in the study. Out of them, 26 were males (65%) and 14 were females (35%). PPHN was most commonly seen in the 29 (72.5%) of participants with a history of first order birth. Mean duration of symptoms was 14.05 ± 2.06 days. The participants were randomized to two groups. Group A consisted of total 25 participants that received both bosentan and sildenafil and group B had 15 participants that received sildenafil alone. Both groups were comparable in terms of birth weight and present weight, consanguinity, and mode of delivery. Efficacy was determined by the reduction in mean baseline Pulmonary Artery Systolic Pressure (PASP). PASP in group A was 75.56 ± 10.62 mm Hg and in group B was 64.86 ± 12.25 mm Hg which was not statistically significant (P > 0.05). PASP on the third and seventh day in group A were 43.72 ± 8.63 and 24.47 ± 3.52 mm Hg compared to 42.28 ± 9.43 and 27.276 ± 8.38 respectively in group B which was statistically significant (P < 0.05).There were two deaths each in both groups. Two participants in Group A developed liver function abnormalities. None of the participants in Group B had adverse effects.

Conclusion: Most common clinical manifestations were nonspecific. Cardiovocal syndrome was common in PPHN. We conclude that oral sildenafil treatment is a safe, simple and effective treatment for persistent pulmonary hypertension in newborn. Combination of bosentan with sildenafil is more effective and safe in reducing pulmonary artery (PA) pressures in high-risk patients with PPHN.