Vasodilator therapy for pulmonary hypertension in children: a national study of patient characteristics and current treatment strategies

Abstract

Pulmonary vasodilator therapy is still often an off-label treatment for pulmonary hypertension in children. The aim of this nationwide register-based study was to assess patient characteristics and strategies for pulmonary vasodilator therapy in young Swedish children. Prescription information for all children below seven years of age at treatment initiation, between 2007-2017, was retrieved from the National Prescribed Drug Register and medical information was obtained by linkage to other registers. All patients were categorized according to the WHO classification of pulmonary hypertension. In total, 233 patients had been prescribed pulmonary vasodilators. The treatment was initiated before 1 year of age in 61% (N=143). Sildenafil was most common (N=224 patients), followed by bosentan (N=29), iloprost (N=14), macitentan (N=4), treprostinil (N=2) and riociguat (N=2). Over the study period the prescription rate for sildenafil tripled. Monotherapy was most common, 87% (N=203), while 13% (N=20) had combination therapy. Bronchopulmonary dysplasia (N=82, 35%) and/or congenital heart defects (CHD; N=156, 67%) were the most common associated conditions. 8% (N=18) of the patients had Down syndrome. Cardiac catheterization had been performed in 39% (N=91). Overall mortality was 13% (N=30) during the study period. This study provides an unbiased overview of national outpatient use of pulmonary vasodilator therapy in young children. Few cases of idiopathic pulmonary arterial hypertension were found, but a large proportion of pulmonary hypertension associated with CHD or bronchopulmonary dysplasia. Despite treatment, mortality was high and additional pediatric studies are needed for a better understanding of underlying pathologies and evidence of treatment effects.

Risk factors for isolated atrial septal defect secundum morbidity

“…Preterm birth, which includes several mediators for overall morbidity has not been assessed previously in relation to ASD II morbidity. We did not include PPHN in our regression analyses, as it may be classified as a mediator of morbidity in children born preterm and is linked to premature birth as well as to Down syndrome 12 , 24 , 25 . Altered pulmonary vascular resistance and delayed normalization of the pulmonary circulation, high pulmonary pressure, along with the intolerance to pulmonary overflow, can indicate that there might be a need of cardiac drug treatment in children with ASDII and maybe especially those with Down syndrome 26 .…”

Navigating Diagnostic and Treatment Challenges of Pulmonary Hypertension in Infants with Bronchopulmonary Dysplasia

“…Sildenafil is currently approved by the Food and Drug Administration (FDA) in children greater than one year of age. It remains the most widely used PH therapy for BPD-PH [ 90 , 91 , 92 ] and study as a possible preventative therapy is being explored [ 93 , 94 ]. Adverse drug effects of GE reflux [ 95 ] are not uncommon in the BPD-PH population and infants should be monitored for this.…”

The vascular phenotype of BPD: new basic science insights—new precision medicine approaches

“…Riociguat, a recently developed GC stimulator demonstrates promising efficacy in preclinical studies. 14,15 Its off-label use has been occasionally reported in children with PH, 16 including case reports that demonstrate efficacy in severe, treatment-resistant PH. 17 It has not yet been tested in infants with BPD-PH.…”