Researchers discovered that the drug riociguat has a biological advantage over both phosphodiesterase-5 inhibitors and inhaled nitric oxide (NO) for patients with bronchopulmonary dysplasia and/or developmental lung disease and chronic pulmonary arterial hypertension (PAH), according to a study published in the Journal of Pediatrics.

“Chronic pulmonary arterial hypertension of the neonate/infant is a serious disorder with implications on morbidity and mortality,” the authors of the study wrote.

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Studies indicate that chronic PAH is present in 6% to 39% of patients with mild to severe bronchopulmonary dysplasia; it is also present in around 2% of preterm patients without bronchopulmonary dysplasia. Patients with bronchopulmonary dysplasia diagnosed with chronic PAH have an extremely poor prognosis; the condition has a 2-year mortality rate of around 47%. 

“Agents with a strong safety profile which lower pulmonary vascular resistance, reverse maladaptive processes, and minimize exposure to polypharmacy would be highly desirable,” the authors of the study wrote. 

Riociguat is a soluble guanylate cyclase (sGC) stimulator that has been shown to improve clinical symptoms in adults with chronic PAH. It has a dual mechanism of action: it both stimulates the reduced form of sGC and increases NO binding to the oxidized form of sGC. Sildenafil, on the other hand, is a phosphodiesterase-5 inhibitor. 

The authors of the study used a clinical database to search for cases of infants treated with riociguat between January 2020 and June 2022. The common approach to treating chronic PAH is to first prescribe an inhaled agent (such as NO) for 2 to 4 weeks. Sildenafil is typically used as a second-line therapy, the failure of which opens up the option of an alternative. In January 2020, oral riociguat was added as an alternative agent for patients who failed sildenafil therapy. 

The research team selected cases of patients who had an echocardiography diagnosis of chronic PAH with at least a 1-week history of riociguat therapy. Ten cases were identified. The researchers discovered that none of the patients had reported episodes of critical hypotension or needed a new or escalated vasopressor. In addition, the researchers discovered that a decline in all components of arterial pressure was noted 2 hours following riociguat therapy, especially with the first doses administered. 

“Instead of providing a source of NO (and associated free-radicals), riociguat increases the sensitivity of sGC to low levels of endogenously produced NO and its dual mechanism of action via stimulation of sGC by nitric oxide dependent and independent has theoretical benefits over both nitrates and [phosphodiesterase-5] inhibitors,” the authors of the study concluded. 


Giesinger RE, Stanford AH, Thomas B, Abman SH, McNamara PJ. Safety and feasibility of riociguat therapy for the treatment of chronic pulmonary arterial hypertension in infancyJ Pediatr. Published online November 30, 2022. doi:10.1016/j.jpeds.2022.11.026