A Randomized Study of Safety and Efficacy of Two Doses of Ambrisentan to Treat Pulmonary Arterial Hypertension in Pediatric Patients Aged 8 Years up to 18 Years

Treprostinil, a prostacyclin analogue, is approved for the treatment of pulmonary arterial hypertension (PAH) in adults. Transition from parenteral to oral treprostinil has been successfully accomplished in adults with PAH but not in children. In this multicenter study, pediatric patients treated with parenteral (Cohort 1) or inhaled (Cohort 2) treprostinil were transitioned to oral treprostinil. Prostacyclin-naïve individuals on background oral PAH therapy received oral treprostinil as add-on therapy (Cohort 3). Successful transition was oral treprostinil dose maintenance through week 24. Patients were monitored for adverse events (AEs), 6-min walk distance (6MWD), PAH symptoms, World Health Organization (WHO) Functional Class (FC), cardiac magnetic resonance imaging (cMRI), cardiopulmonary exercise testing (CPET), and quality of life through 24 weeks. A total of 32 patients were enrolled in the study; 23 (72%) were girls (mean age = 12.2 years). All patients were on background oral PAH therapy. Overall, patients (96.9%) maintained transition to oral treprostinil; one patient (Cohort 1) transitioned to oral treprostinil, then back to parenteral after experiencing syncope and WHO FC change from II to III. Cohorts 1, 2, and 3 received a final mean oral treprostinil dose of 5.6, 3.3, and 4.5 mg t.i.d., respectively. All cohorts had variable changes in 6MWD, cMRI, and CPET. Overall, 12 serious AEs were reported. All patients had drug-related AEs including headache (81%), diarrhea (69%), nausea (66%), vomiting (66%), and flushing (56%). Pediatric patients maintained transition to oral treprostinil with preservation of exercise capacity and WHO FC. Prostanoid-related AEs were most common and similar to those reported in adults.

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Safety and efficacy of transitioning from the combination of bosentan and sildenafil to alternative therapy in patients with pulmonary arterial hypertension

Pulmonary Circulation ◽

10.1177/2045894020945523 ◽

2020 ◽

Vol 10 (4) ◽

pp. 204589402094552

Author(s):

Nathan J. Verlinden ◽

Raymond L. Benza ◽

Amresh Raina

Keyword(s):

Drug Interaction ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Alternative Therapy ◽

Functional Class ◽

World Health ◽

Risk Scores ◽

Safety And Efficacy ◽

Significant Drug Interaction ◽

Pulmonary Arterial

The combination of bosentan and sildenafil is commonly used to treat patients with pulmonary arterial hypertension (PAH); however, there is evidence of a significant drug interaction between these two medications. We sought to evaluate the safety and efficacy of transitioning patients with PAH from the combination of bosentan and sildenafil to alternative therapy. A retrospective database review was performed on 16 patients with PAH who were treated with the combination of bosentan and sildenafil and transitioned to alternative treatment at our center. Invasive and non-invasive patient parameters were collected at baseline and after transition. 56.3% of patients were in World Health Organization functional class (WHO FC) III and a majority of patients (68.7%) were on background prostacyclin therapy. The most common reason for transition was concern for a drug interaction in seven patients (43.8%). The most common transition was bosentan to macitentan in eight patients (50%). Fifteen patients (93.8%) tolerated the transition after a median follow-up of 6.5 months with minor adverse events occurring in four patients (25%). In 11 patients, 6-min walk distance (6MWD) was unchanged comparing baseline to post transition measurements with a median change of +8 m (range: −50 to + 70; P = 0.39). Nine patients (81.8%) had stable (within 15% margin) or significant improvement (increase by ≥15%) in 6MWD after transition. All patients demonstrated stable or improved WHO FC after transition. There were no significant changes after transition in hemodynamics, N-terminal pro-brain natriuretic peptide (NT-proBNP) values, or Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk scores. In our study, transitioning patients from bosentan and sildenafil to alternative therapy was safe and resulted in clinical stability.

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SAFETY AND EFFICACY OF MACITENTAN IN ELDERLY PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION (PAH): INSIGHTS FROM SERAPHIN

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(20)32717-0 ◽

2020 ◽

Vol 75 (11) ◽

pp. 2090

Author(s):

David Langleben ◽

Richard Channick ◽

Marion Delcroix ◽

Nazzareno Galiè ◽

Ardeschir Ghofrani ◽

...

Keyword(s):

Pulmonary Arterial Hypertension ◽

Elderly Patients ◽

Arterial Hypertension ◽

Safety And Efficacy ◽

Pulmonary Arterial

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Quality of Life, Safety and Efficacy Profile of Thermostable Flolan in Pulmonary Arterial Hypertension

PLoS ONE ◽

10.1371/journal.pone.0120657 ◽

2015 ◽

Vol 10 (3) ◽

pp. e0120657 ◽

Cited By ~ 6

Author(s):

Steeve Provencher ◽

Patrap Paruchuru ◽

Andrea Spezzi ◽

Brian Waterhouse ◽

Mardi Gomberg-Maitland ◽

...

Keyword(s):

Quality Of Life ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Life Safety ◽

Safety And Efficacy ◽

Pulmonary Arterial ◽

Efficacy Profile

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Where the congenital heart disease meets the pulmonary arterial hypertension, FLNA matters: a case report and literature review

BMC Pediatrics ◽

10.1186/s12887-020-02393-2 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Xiaoxian Deng ◽

Shanshan Li ◽

Qiu Qiu ◽

Bowen Jin ◽

Menghuan Yan ◽

...

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Congenital Heart ◽

Pediatric Patients ◽

De Novo ◽

Wide Spectrum ◽

Heart Defects ◽

Pulmonary Arterial

Abstract Background Pediatric patients with genetic disorders have a higher incidence of pulmonary arterial hypertension (PAH) regardless of their heart defects. Filamin A (FLNA) mutation is recently recognized to be associated with pediatric pulmonary disorders, however, the clinical courses of PAH related to the mutation were reported in limited cases. Here, we presented a case and pooled data for better understanding of the correlation between FLNA mutation and pediatric PAH. Case presentation The patient was a 8-month-old female with repeated episodes of pneumonia. Physical examination revealed cleft lip, cleft palate and developmental retardation. Imaging examination showed a small atrial septal defect (ASD), central pulmonary artery enlargement, left upper lobe of lung atelectasis, and pulmonary infiltration. Genetic test showed she carried a de novo pathogenic variant of FLNA gene (c.5417-1G > A, p.-). Oral medications didn’t slow the progression of PAH in the patient, and she died two years later. Conclusions FLNA mutation causes rare but progressive PAH in addition to a wide spectrum of congenital heart disease and other comorbidities in pediatric patients. We highly recommend genetic testing for pediatric patients when suspected with PAH. Given the high mortality in this group, lung transplantation may offer a better outcome.

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