scholarly journals An Advanced Protocol-Driven Transition from Parenteral Prostanoids to Inhaled Trepostinil in Pulmonary Arterial Hypertension

2016 ◽  
Vol 6 (4) ◽  
pp. 532-538 ◽  
Author(s):  
Ronald Oudiz ◽  
Manyoo Agarwal ◽  
Franz Rischard ◽  
Teresa De Marco
Keyword(s):  
New York ◽  
Pulmonary Arterial Hypertension ◽  
Adverse Events ◽  
Arterial Hypertension ◽  
Heart Association ◽  
Functional Class ◽  
Inclusion Criteria ◽  
Serious Adverse Events ◽  
New York Heart Association ◽  
Pulmonary Arterial

Patients with pulmonary arterial hypertension (PAH) often require parenteral prostanoids to improve symptoms and signs of PAH. Complications of parenteral prostanoids—such as catheter-related infections and intolerable adverse effects—may develop, prompting transition to inhaled prostanoids. We report a prospective, protocol-driven transition from parenteral prostanoids to inhaled prostanoids with monitoring of exercise gas exchange and acute hemodynamics. Three PAH centers recruited patients transitioning from parenteral prostanoids to inhaled trepostinil. Rigid inclusion criteria were used, including parenteral prostanoid dose < 30 ng/kg/min, New York Heart Association functional class (FC) < 3, and pulmonary vascular resistance (PVR) < 6 Wood units. Of the 9 patients meeting initial inclusion criteria, 3 were excluded. In the remaining patients, the parenteral prostanoid was reduced and the inhaled prostanoid was increased over 24–36 hours with continuous hemodynamic monitoring. Exercise capacity and FC were measured at baseline and weeks 1, 4, and 12. All patients were successfully weaned from parenteral prostanoids. An acute PVR decrease was seen with most inhaled prostanoid doses, but PVR varied throughout the transition. Patients tolerated inhaled prostanoids for 9–12 breaths 4 times a day with no treatment-limiting adverse events. At week 12, FC was unchanged, and all patients continued to receive inhaled prostanoids without serious adverse events or additional PAH therapy. In 5 of 6 patients, 6-minute walk distance and peak V̇O2 were within 10% of baseline. Using a strict transition protocol and rigid patient selection criteria, the parenteral prostanoid to inhaled prostanoid transition appeared safe and well tolerated and did not result in clinical deterioration over 12 weeks. Hemodynamic variability noted acutely during transition in our study did not adversely affect successful transition. (Trial registration: ClinicalTrials.gov identifier: NCT01268553)

Inhaled Treprostinil for the Treatment of Pulmonary Arterial Hypertension

2011 ◽  
Vol 31 (6) ◽  
pp. e1-e10 ◽  
Author(s):  
Abby Poms ◽  
Martha Kingman
Keyword(s):  
New York ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Severe Disease ◽  
Pulmonary Arteries ◽  
Heart Association ◽  
Functional Class ◽  
Class Iii ◽  
New York Heart Association ◽  
Pulmonary Arterial

Pulmonary arterial hypertension is a progressive disease characterized by vascular proliferation and vasoconstriction of the small pulmonary arteries that eventually leads to right-sided heart failure and death. Patients often initially have symptoms such as shortness of breath, fatigue, and edema; later in the disease, presyncope and syncope are common. Patients with progressive pulmonary arterial hypertension despite oral therapy and/or with severe disease typically require treatment with a prostanoid. Inhaled treprostinil (Tyvaso) is a prostacyclin analog indicated for the treatment of pulmonary arterial hypertension to increase walk distance in patients with symptoms classified as New York Heart Association functional class III. Inhaled treprostinil was approved by the Food and Drug Administration in July 2009. This article provides a brief overview of the pathophysiology of pulmonary arterial hypertension and reviews the mechanism of action, key clinical data, and the practical management of inhaled treprostinil in patients with pulmonary arterial hypertension.

scholarly journals Phenotype and outcome of pulmonary arterial hypertension patients carrying a TBX4 mutation

2020 ◽  
Vol 55 (5) ◽  
pp. 1902340 ◽  
Author(s):  
Pierre Thoré ◽  
Barbara Girerd ◽  
Xavier Jaïs ◽  
Laurent Savale ◽  
Maria-Rosa Ghigna ◽  
...  
Keyword(s):  
New York ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Survival Rates ◽  
Heart Association ◽  
Lung Parenchyma ◽  
Functional Class ◽  
Class Iii ◽  
High Resolution Computed Tomography ◽  
Pulmonary Arterial

IntroductionTBX4 mutation causes small patella syndrome (SPS) and/or pulmonary arterial hypertension (PAH). The characteristics and outcomes of PAH associated with TBX4 mutations are largely unknown.MethodsWe report the clinical, functional, radiologic, histologic and haemodynamic characteristics and outcomes of heritable PAH patients carrying a TBX4 mutation from the French pulmonary hypertension (PH) network.Results20 patients were identified in 17 families. They were characterised by a median age at diagnosis of 29 years (0–76 years) and a female to male ratio of three. Most of the patients (70%) were in New York Heart Association (NYHA) functional class III or IV with a severe haemodynamic impairment (median pulmonary vascular resistance (PVR) of 13.6 (6.2–41.8) Wood units). Skeletal signs of SPS were present in 80% of cases. Half of the patients had mild restrictive or obstructive limitation and diffusing capacity of the lung for carbon monoxide (DLCO) was decreased in all patients. High-resolution computed tomography (HRCT) showed bronchial abnormalities, peri-bronchial cysts, mosaic distribution and mediastinal lymphadenopathies. PAH therapy was associated with significant clinical improvement. At follow-up (median 76 months), two patients had died and two had undergone lung transplantation. One-year, three-year and five-year event-free survival rates were 100%, 94% and 83%, respectively. Histologic examination of explanted lungs revealed alveolar growth abnormalities, major pulmonary vascular remodelling similar to that observed in idiopathic pulmonary arterial hypertension (IPAH) and accumulation of cholesterol crystals within the lung parenchyma.ConclusionPAH due to TBX4 mutations may occur with or without skeletal abnormalities across a broad age range from birth to late adulthood. PAH is usually severe and associated with bronchial and parenchymal abnormalities.

scholarly journals Initial dual oral combination therapy in pulmonary arterial hypertension

2016 ◽  
Vol 47 (6) ◽  
pp. 1727-1736 ◽  
Author(s):  
Olivier Sitbon ◽  
Caroline Sattler ◽  
Laurent Bertoletti ◽  
Laurent Savale ◽  
Vincent Cottin ◽  
...  
Keyword(s):  
New York ◽  
Pulmonary Arterial Hypertension ◽  
Combination Therapy ◽  
Arterial Hypertension ◽  
Single Agent ◽  
Survival Rates ◽  
Heart Association ◽  
Functional Class ◽  
Class Iii ◽  
Pulmonary Arterial

Treatment for pulmonary arterial hypertension (PAH) has been underpinned by single-agent therapy to which concomitant drugs are added sequentially when pre-defined treatment goals are not met.This retrospective analysis of real-world clinical data in 97 patients with newly diagnosed PAH (86% in New York Heart Association functional class III−IV) explored initial dual oral combination treatment with bosentan plus sildenafil (n=61), bosentan plus tadalafil (n=17), ambrisentan plus tadalafil (n=11) or ambrisentan plus sildenafil (n=8).All regimens were associated with significant improvements in functional class, exercise capacity, dyspnoea and haemodynamic indices after 4 months of therapy. Over a median follow-up period of 30 months, 75 (82%) patients were still alive, 53 (71%) of whom received only dual oral combination therapy. Overall survival rates were 97%, 94% and 83% at 1, 2 and 3 years, respectively, and 96%, 94% and 84%, respectively, for the patients with idiopathic PAH, heritable PAH and anorexigen-induced PAH. Expected survival rates calculated from the French equation for the latter were 86%, 75% and 66% at 1, 2 and 3 years, respectively.Initial combination of oral PAH-targeted medications may offer clinical benefits, especially in PAH patients with severe haemodynamic impairment.

scholarly journals Recommendations for the clinical management of patients receiving macitentan for pulmonary arterial hypertension (PAH): A Delphi consensus document

2017 ◽  
Vol 7 (3) ◽  
pp. 702-711 ◽  
Author(s):  
Franck F. Rahaghi ◽  
Hassan M. Alnuaimat ◽  
Rana L.A. Awdish ◽  
Vijay P. Balasubramanian ◽  
Robert C. Bourge ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Adverse Events ◽  
Arterial Hypertension ◽  
Functional Class ◽  
Event Management ◽  
Delphi Consensus ◽  
Consensus Recommendations ◽  
Modified Delphi ◽  
Consensus Document ◽  
Pulmonary Arterial

In patients treated with macitentan (Opsumit®, Actelion Pharmaceuticals Ltd., Basel, Switzerland) for pulmonary arterial hypertension (PAH), prevention and/or effective management of treatment-related adverse events may improve adherence. However, management of these adverse events can be challenging and the base of evidence and clinical experience for macitentan is limited. In the absence of evidence, consensus recommendations from physicians experienced in using macitentan to treat PAH may benefit patients and physicians who are using macitentan. Consensus recommendations were developed by a panel of physicians experienced with macitentan and PAH using a modified Delphi process. Over three iterations, panelists developed and refined a series of statements on the use of macitentan in PAH and rated their agreement with each statement on a Likert scale. The panel of 18 physicians participated and developed a total of 118 statements on special populations, add-on therapy, drug–drug interactions, warnings and precautions, hospitalization and functional class, and adverse event management. The resulting consensus recommendations are intended to provide practical guidance on real-world issues in using macitentan to treat patients with PAH.

Inhaled Iloprost in Pulmonary Arterial Hypertension

2005 ◽  
Vol 39 (7-8) ◽  
pp. 1265-1274 ◽  
Author(s):  
Stacey E Baker ◽  
Rebecca Haynes Hockman
Keyword(s):  
Clinical Trials ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Data Extraction ◽  
Controlled Trial ◽  
Heart Association ◽  
Functional Class ◽  
Medline Search ◽  
Inhaled Iloprost ◽  
Pulmonary Arterial

OBJECTIVE To review the pharmacology, pharmacodynamics, and clinical trials evaluating inhaled iloprost in pulmonary arterial hypertension (PAH). DATA SOURCES A MEDLINE search (1996–February 2005) was performed using the key words pulmonary hypertension, iloprost, and epoprostenol. Information regarding Food and Drug Administration approval was obtained via the Internet. STUDY SELECTION AND DATA EXTRACTION All clinical trials using inhaled iloprost in PAH published in English were identified. Additionally, references from the identified articles were reviewed. DATA SYNTHESIS A stable analog of prostacyclin, inhaled iloprost is thought to promote benefit in PAH through vasodilation, antiproliferative effects, and inhibition of platelet aggregation. In a placebo-controlled trial of 203 patients, inhaled iloprost significantly improved the combined endpoint of change in New York Heart Association functional class and 10% improvement in 6-minute walk distance (p = 0.007). Small, short-term clinical trials demonstrated hemodynamic benefits for inhaled iloprost alone and in combination with other pulmonary vasodilating agents. The aerosolized delivery route and low incidence of adverse events are positive attributes for inhaled iloprost, while the frequency of administration and lack of comparative data limit its role in PAH. CONCLUSIONS Currently, inhaled iloprost offers potential benefit for patients with contraindications to bosentan, preference for non-parenteral products, ineligibility for parenteral therapy, or as adjunctive therapy with other pulmonary vasodilators. Larger, long-term clinical trials are needed to solidify the role for inhaled iloprost in the management of PAH.

scholarly journals Addition of Sildenafil in Patients with Pulmonary Arterial Hypertension with Inadequate Response to Bosentan Monotherapy

2008 ◽  
Vol 15 (8) ◽  
pp. 427-430 ◽  
Author(s):  
Nancy R Porhownik ◽  
Hassan Al-Sharif ◽  
Zoheir Bshouty
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Combination Therapy ◽  
Arterial Hypertension ◽  
Exercise Tolerance ◽  
Nyha Class ◽  
Heart Association ◽  
Functional Class ◽  
Inadequate Response ◽  
Nyha Classification ◽  
Pulmonary Arterial

BACKGROUND: Pulmonary arterial hypertension (PAH) remains a progressive disease despite improvement when using one of three medication classes: prostanoids, endothelin receptor antagonists or phosphodiesterase-5 inhibitors. Combination therapy has been proposed for patients with unsatisfactory response to monotherapy.OBJECTIVES: To examine the effect of adding sildenafil to bosentan on 6 min walk distance (6MWD) and New York Heart Association (NYHA) classification in patients with PAH who achieved inadequate improvement with bosentan monotherapy.METHODS: Patients with idiopathic PAH or connective tissue disease-associated PAH, and who had either self-reported inadequate improvement in exercise tolerance or a decline in 6MWD after initial improvement, were included in the study (n=10). Data on 6MWD and NYHA class at baseline (before initiation of bosentan), three and six months after baseline, second baseline (before initiation of combination therapy with sildenafil), and three and six months after second baseline were analyzed for any changes.RESULTS: Mean time from initiation of bosentan monotherapy to initiation of combination therapy was 558 days (range 150 to 900 days). Six months after initiation of bosentan, 6MWD increased by 57.2 m above the baseline of 314.4 m. Six months after combination therapy, 6MWD was 62.80 m higher than the baseline before initiation of combination therapy of 339 m (P<0.02). The overall increase in 6MWD six months after combination therapy was higher than the first baseline by 87.4 m (P not significant). NYHA functional class did not improve with combination therapy in all patients.DISCUSSION: Initiating combination therapy in patients who achieve an inadequate improvement in exercise tolerance with mono-therapy may result in further improvement in exercise tolerance.

scholarly journals Long-term outcomes of dasatinib-induced pulmonary arterial hypertension: a population-based study

2017 ◽  
Vol 50 (1) ◽  
pp. 1700217 ◽  
Author(s):  
Jason Weatherald ◽  
Marie-Camille Chaumais ◽  
Laurent Savale ◽  
Xavier Jaïs ◽  
Andrei Seferian ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Heart Association ◽  
Functional Class ◽  
Class Iii ◽  
Long Term Outcomes ◽  
Right Heart Catheterisation ◽  
Pulmonary Arterial

This study aimed to describe the long-term outcomes of pulmonary arterial hypertension (PAH) induced by dasatinib.21 incident, right heart catheterisation-confirmed cases of dasatinib-induced PAH were identified from the French Pulmonary Hypertension Registry. Clinical and haemodynamic variables were compared from baseline to last follow-up (median (range) 24 (1–81) months).Median age was 52 years and 15 patients were female (71%). 19 patients received dasatinib for chronic myelogenous leukaemia for a median (range) duration of 42 (8–74) months before PAH diagnosis. No bone morphogenic protein receptor-2 (BMPR2) mutations were found in the 10 patients tested. Dasatinib was uniformly discontinued and 11 patients received PAH medications. Four patients died during follow-up. New York Heart Association functional class improved from 76% in class III/IV to 90% in class I/II (p<0.01). Median (range) 6-min walk distance improved from 306 (0–660) to 430 (165–635) m (p<0.01). Median (range) mean pulmonary arterial pressure improved from 45 (30–70) to 26 (17–50) mmHg (p<0.01) and pulmonary vascular resistance from 6.1 (3.2–27.3) to 2.6 (1.2–5.9) Wood units (p<0.01). Patients treated with PAH medications had worse baseline haemodynamics but similar long-term outcomes to untreated patients. PAH persisted in 37% of patients.Dasatinib-induced PAH frequently improves after discontinuation but persisted in over one-third of patients, therefore systematic follow-up is essential.

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