Inhaled Iloprost for Severe Pulmonary Hypertension

Olschewski, Horst; Simonneau, Gérald; Galiè, Nazzareno; Higenbottam, T. W.; Naeije, Robert; Rubin, Lewis J.; Nikkho, Sylvia; Speich, Rudolf; Hoeper, Marius M.; Behr, Jürgen; Winkler, Jörg; Sitbon, Olivier; Popov, Wladimir; Ghofrani, Hossein Ardeschir; Manes, Alessandra; Kiely, David G.; Ewert, R.; Meyer, Andreas; Corris, Paul A.; Delcroix, Marion; Gómez-Sánchez, Miguel Ángel; Siedentop, Harald; Seeger, Werner

doi:10.1056/nejmoa020204

Cited by 1,534 publications

(533 citation statements)

References 25 publications

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“…Iloprost is administered by nebulization 6 to 9 times a day and requires patient cooperation, with treatment administration lasting 10 to 15 minutes, which is difficult for young children. 294,326,327 The advantage of an inhaled PGI 2 is that it can cause pulmonary vasodilation with minimal effect on systemic blood pressure. 327, 328 An increase in airway reactivity has been noted in some children receiving inhaled iloprost.…”

Section: Pgi 2 Analogsmentioning

confidence: 99%

Pediatric Pulmonary Hypertension

Abman¹,

Hansmann²,

Archer³

et al. 2015

Circulation

913

405

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Abstract-Pulmonary hypertension is associated with diverse cardiac, pulmonary, and systemic diseases in neonates, infants, and older children and contributes to significant morbidity and mortality. However, current approaches to caring for pediatric patients with pulmonary hypertension have been limited by the lack of consensus guidelines from experts in the field. In a joint effort from the American Heart Association and American Thoracic Society, a panel of experienced clinicians and clinician-scientists was assembled to review the current literature and to make recommendations on the diagnosis, evaluation, and treatment of pediatric pulmonary hypertension. This publication presents the results of extensive literature reviews, discussions, and formal scoring of recommendations for the care of children with pulmonary hypertension. Key Words: AHA Scientific Statements ◼ bronchopulmonary dysplasia ◼ congenital diaphragmatic hernia ◼ congenital heart disease ◼ genetics ◼ persistent pulmonary hypertension of the newborn ◼ sickle cell disease © 2015 by the American Heart Association, Inc., and the American Thoracic Society.Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIR.0000000000000329 †Deceased. The American Heart Association and the American Thoracic Society make every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.This document was approved by the American Heart Association Science Advisory and Coordinating Committee on May 12, 2015, the American Heart Association Executive Committee on July 22, 2015, and the American Thoracic Society on July 24, 2015.The online-only Data Supplement is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIR.0000000000000329/-/DC1. The American Heart Association requests that this document be cited as follows: Abman SH, Hansmann G, Archer SL, Ivy DD, Adatia I, Chung WK, Hanna BD, Rosenzweig EB, Raj JU, Cornfield D, Stenmark KR, Steinhorn R, Thébaud B, Fineman JR, Kuehne T, Feinstein JA, Friedberg MK, Earing M, Barst RJ, Keller RL, Kinsella JP, Mullen M, Deterding R, Kulik T, Mallory G, Humpl T, Wessel DL; on behalf of the American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation, Council on Clinical Cardiology, Council on Cardiovascular Disease in the Young, Council on Cardiovascular Radiology and Intervention, Council on Cardiovascular Surgery and Anesthesia, and the American Thoracic Society. Pediatric pulmonary hypertension: guidelines from the American Heart Association and American Thoracic Society. Circulation. 2015;132:2037-2099 Copies: This document is available on the World Wide Web site of the American Heart Associat...

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Section: Pgi 2 Analogsmentioning

confidence: 99%

Pediatric Pulmonary Hypertension

Abman¹,

Hansmann²,

Archer³

et al. 2015

Circulation

913

405

View full text Add to dashboard Cite

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“…7,13,15,16 There was no evidence of previously unidentified, treatment-limiting, oral administrationspecific AEs. It appears that the 0.25-mg BID starting dose in the mITT population was better tolerated (lower rate of discontinuation in the mITT population than in the ITT population, many of whom started on 1 mg BID).…”

Section: Discussionmentioning

confidence: 96%

“…1,8,11 In fact, inhaled prostacyclin analogues have emerged as attractive treatment options, especially as part of second-line combination therapies, because of their relatively low incidence of systemic side effects and relative ease of use compared with parenteral therapy. [12][13][14][15][16][17] The development of effective oral prostacyclin analogues, however, has proven more challenging. Although the initial clinical results for the first-in-class oral prostacyclin beraprost were encouraging, follow-up studies were unsuccessful, and the compound never gained regulatory approval in the United States or Europe.…”

mentioning

confidence: 99%

Efficacy and Safety of Oral Treprostinil Monotherapy for the Treatment of Pulmonary Arterial Hypertension

et al. 2013

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Background-Pulmonary arterial hypertension (PAH) is a progressive, fatal disease with no cure. Parenteral and inhaled prostacyclin analogue therapies are effective for the treatment of PAH, but complicated administration requirements can limit the use of these therapies in patients with less severe disease. This study was designed to evaluate the safety and efficacy of the oral prostacyclin analogue treprostinil diolamine as initial treatment for de novo PAH. Methods and Results-Three hundred forty-nine patients (intent-to-treat population) not receiving endothelin receptor antagonist or phosphodiesterase type-5 inhibitor background therapy were randomized (treprostinil, n=233; placebo, n=116). The primary analysis population (modified intent-to-treat) included 228 patients (treprostinil, n=151; placebo, n=77) with access to 0.25-mg treprostinil tablets at randomization. The primary end point was change from baseline in 6-minute walk distance at week 12. Secondary end points included Borg dyspnea index, clinical worsening, and symptoms of PAH. The week 12 treatment effect for 6-minute walk distance (modified intent-to-treat population) was 23.0 m (P=0.0125). For the intent-to-treat population, 6-minute walk distance improvements were observed at peak (26.0 m; P=0.0001) and trough (17.0 m; P=0.0025) plasma study drug concentrations. Other than an improvement in the combined 6-minute walk distance/Borg dyspnea score, there were no significant changes in secondary end points. Oral treprostinil therapy was generally well tolerated; the most common adverse events (intent-to-treat) were headache (69%), nausea (39%), diarrhea (37%), and pain in jaw (25%). Conclusions-Oral treprostinil improves exercise capacity in PAH patients

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“…The same agents regulate pulmonary vascular tone and are currently employed for treatment of pulmonary hypertension, a devastating disease impairing exercise capacity, quality of life and life expectancy [3]. New treatment concepts in pulmonary hypertension include both local administration of agents, such as inhalation of NO and the stable prostacyclin analogue iloprost, and systemic delivery of different vasodilatory prostanoids and the PDE-5 inhibitor sildenafil [4,5,6,7,8,9]. However, investigations addressing the effects of these lung treatment strategies on features of cerebral microcirculatory regulation have not yet been performed.…”

Section: Introductionmentioning

confidence: 99%

Sildenafil Improves Dynamic Vascular Function in the Brain: Studies in Patients with Pulmonary Hypertension

et al. 2006

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Background: Prostaglandins and nitric oxide play a pivotal role in the regulation of macro- and microcirculatory blood flow distribution. Interference with both mediator systems have been implicated in cerebrovascular dysfunction. Inhaled iloprost (long-acting prostacyclin analogue) and the phosphodiesterase-5 inhibitor sildenafil have recently shown efficacy in the treatment of chronic pulmonary hypertension. We investigated the impact of these agents on cerebral microcirculatory regulation in patients suffering from this disease. Methods: In 11 patients suffering from severe pulmonary hypertension, a functional transcranial Doppler test utilizing a visual stimulation paradigm was undertaken to measure the evoked flow velocity in the posterior cerebral artery. Measurements were performed in parallel to right heart catheterization and pharmacological testing of the pulmonary vasoreactivity. After assessment of baseline measurements, inhaled iloprost and oral sildenafil were given consecutively for testing of cerebral and pulmonary vascular function. The data gained from the Doppler measurements were compared to data from 22 healthy volunteers. Results: Both substances provoked a significant reduction of pulmonary arterial pressure and vascular resistance, accompanied by minor changes in systemic vascular resistance. In contrast to these superimposable hemodynamic profiles opposite effects were observed regarding cerebral vascular tone: cerebral microvascular reactivity, as assessed by attenuation and time rate parameters, was significantly improved by sildenafil, but slightly worsened by iloprost. Conclusions: Sildenafil has beneficial effects on cerebral vascular reactivity indicative of an improvement in neurovascular coupling in patients with pulmonary hypertension. These results warrant further investigations of the influence of sildenafil on dynamic vascular function in the brain independent of the underlying disease.

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Inhaled Iloprost for Severe Pulmonary Hypertension

Cited by 1,534 publications

References 25 publications

Pediatric Pulmonary Hypertension

Pediatric Pulmonary Hypertension

Efficacy and Safety of Oral Treprostinil Monotherapy for the Treatment of Pulmonary Arterial Hypertension

Sildenafil Improves Dynamic Vascular Function in the Brain: Studies in Patients with Pulmonary Hypertension

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