Aerosolized Iloprost Therapy Could Not Replace Long-term IV Epoprostenol (Prostacyclin) Administration in Severe Pulmonary Hypertension

Schenk, Peter; Petkov, Ventzislav; Madl, Christian; Kramer, Ludwig; Kneußl, Meinhard; Ziesche, Rolf; Lang, Irene M.

doi:10.1378/chest.119.1.296

Cited by 41 publications

(18 citation statements)

References 17 publications

(23 reference statements)

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“…Moreover, there are also some attempts to use other ways of administering the drug in this setting: it has been suggested that aerosolised iloprost has sustained effects on exercise capacity and pulmonary haemodynamics in patients with primary PH [35], but other studies have not confirmed these results or have failed to demonstrate that this approach could replace long-term i.v. epoprostenol in these patients [36,37]. The optimal dose, method of aerosol administration and a possible use of combination protocols also remain to be determined.…”

Section: Discussionmentioning

confidence: 99%

Systemic Sclerosis Therapy with Iloprost: A Prospective Observational Study of 30 Patients Treated for a Median of 3 Years

Bettoni¹,

Geri²,

Airò³

et al. 2002

Clin Rheumatol

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Iloprost is useful in the short-term treatment of severe Raynaud's phenomenon and ischaemic ulcers in patients with systemic sclerosis (SSc), but its long-term effects are largely unknown. The aim of this study was to report long-term outcome (median follow-up 36 months) in a prospective observational study of a cohort of 30 consecutive patients with SSc who received iloprost therapy with maintenance infusions every 3 weeks after an initial cycle of 5 consecutive days. At the end of the observation, compared to the pretreatment point, we observed complete healing of digital ulcers in 19/21 patients (90%), a decrease of the Raynaud's phenomenon visual analogue score from 10/10 (25th-75th percentile 7-10) to 5/10 (4-6.75) ( P <0.001) and, in patients with diffuse cutaneous involvement, of the modified Rodnan skin thickness score from 25.5 (16.5-31.5) to 16 (13.5-20) ( P = 0.02), minimal improvement of the Health Assessment Questionnaire from 0.87 (0.68-1.37) to 0.75 (0.62-1.25), which was neither statistically nor clinically significant. The forced vital capacity was not significantly changed, but the diffusion capacity corrected for the alveolar volume decreased from 71% (54-76.7) of the expected value to 62% (51.5-71) ( P = 0.02). In one patient with limited SSc a positive effect on pulmonary hypertension was observed. Six patients, after a median of 25 months of treatment and healing of digital ulcers, discontinued the therapy; after a median of 10 months ulcers did not recur in five of these six. Other reasons for discontinuation were: tolerability (1), disease progression (normotensive renal crisis: 1), and death due to intracranial haemorrhage (1). This same patient had previously suffered a central retinal vein thrombosis. In conclusion, long-term therapy with iloprost in patients with SSc has a durable effectiveness on ischaemic ulcers and Raynaud's phenomenon, but it is not possible to conclude that the natural history of the disease was modified.

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Section: Discussionmentioning

confidence: 99%

Systemic Sclerosis Therapy with Iloprost: A Prospective Observational Study of 30 Patients Treated for a Median of 3 Years

Bettoni¹,

Geri²,

Airò³

et al. 2002

Clin Rheumatol

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“…In another report, mono-therapy with aerosolized iloprost failed to replace long-term IV epoprostenol administration in three patients with severe pulmonary hypertension who were classified as WHO class II while on treatment with continuous epoprostenol infusion (10-16 ng/ kg/min) [25]. Two of these patients had IPAH and one of them showed a positive response to inhaled iloprost (mean PAP decreased from 87 to 44 mmHg, PVR from 1717 to 486 dyn s sec -5 and cardiac output increased from 3.7 to 6.3 l/min).…”

Section: Discussionmentioning

confidence: 98%

Erfolgreiche Umstellung einer intravenösen Langzeittherapie mit Iloprost auf eine nicht invasive Kombinationstherapie bei idiopathischer pulmonal arterieller Hypertonie

Halank¹,

Kolditz²,

Opitz³

et al. 2006

Wien Klin Wochenschr

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In Europe intravenous (IV) iloprost, an alternative to epoprostenol, is an accepted treatment option for severely compromised patients with idiopathic pulmonary arterial hypertension (IPAH). Once initiated, this therapy usually has to be continued lifelong or as bridging to transplantation. In our paper we describe two patients with IPAH in World Health Organisation (WHO) functional classes II and III while on treatment with continuous IV iloprost monotherapy or combination therapy with continuous IV iloprost plus oral bosentan, respectively. The duration of IV iloprost therapy was 4.5 and 2.5 years, respectively. Because of life-threatening or recurring catheter-related complications during long-term IV iloprost therapy, these patients were switched to non-invasive combination therapy consisting of oral bosentan plus aerosolized iloprost (patient 1) and oral bosentan plus aerosolized iloprost plus oral sildenafil (patient 2), respectively. After four weeks of additional bosentan therapy, stepwise reduction and discontinuation of IV iloprost were performed within eight hours in the patient in WHO class II, and within five days in the patient in WHO class III. Simultaneously, therapy with aerosolized iloprost was started in the first patient and with aerosolized iloprost plus sildenafil in the second patient. Both patients were safely switched from IV iloprost to non-invasive combination therapy while WHO classification of functional status remained unchanged for at least 12 and 14 months, respectively. These data suggest that selected patients with complications due to IV iloprost treatment can be safely switched to non-IV combination therapies.

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“…In contrast, two uncontrolled studies in patients observed a lack of efficacy of inhaled iloprost. Schenk and coworkers [111] tried to replace i.v. epoprostenol in 3 patients (NYHA II after 4 years of continuous application) by inhaled iloprost.…”

Section: Long-term Effects and Outcome Studiesmentioning

confidence: 99%

Searching the Ideal Inhaled Vasodilator: From Nitric Oxide to Prostacyclin

et al. 2002

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Today, the technique to directly administer vasodilators via the airway to treat pulmonary hypertension and to improve pulmonary gas exchange is widely accepted among clinicians. The flood of scientific work focussing on this new therapeutic concept had been initiated by a fundamental new observation by Pepke-Zaba [1]and Frostell in 1991 [2]: Both scientists reported, that inhalation of exogenous nitric oxide (NO) gas selectively dilates pulmonary vessels without a concomittant systemic vasodilation. No more than another decade ago NO was identified as an important endogenous vasodilator [3]while having merely been regarded an environmental pollutant before that time. Although inhaled NO proved to be efficacious, alternatives were sought-after due to NO’s potential side-effects. In search for the ideal inhaled vasodilator another group of endogenous mediators – the prostanoids – came into the focus of interest. The evidence for safety and efficacy of inhaled prostanoids is – among a lot of other valuable work – based on a series of experimental and clinical investigations that have been performed or designed at the Institute for Surgical Research under the guidance and mentorship of Prof. Dr. med. Dr. h.c. mult. K. Messmer [4-19]. In the following, the current and newly emerging clinical applications of inhaled prostanoids and the experimental data which they are based on, will be reviewed.

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Aerosolized Iloprost Therapy Could Not Replace Long-term IV Epoprostenol (Prostacyclin) Administration in Severe Pulmonary Hypertension

Cited by 41 publications

References 17 publications

Systemic Sclerosis Therapy with Iloprost: A Prospective Observational Study of 30 Patients Treated for a Median of 3 Years

Systemic Sclerosis Therapy with Iloprost: A Prospective Observational Study of 30 Patients Treated for a Median of 3 Years

Erfolgreiche Umstellung einer intravenösen Langzeittherapie mit Iloprost auf eine nicht invasive Kombinationstherapie bei idiopathischer pulmonal arterieller Hypertonie

Searching the Ideal Inhaled Vasodilator: From Nitric Oxide to Prostacyclin

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