Efficacy and Safety of Inhaled Iloprost in Japanese Patients With Pulmonary Arterial Hypertension　– Insights From the IBUKI and AIR Studies –

Saji, Tsutomu; Myoishi, Masafumi; Sugimura, Koichiro; Tahara, Nobuhiro; Takeda, Yutaka; Fukuda, Keiichi; Olschewski, Horst; Matsuda, Yoshinobu; Nikkho, Sylvia; Satoh, Tsuyoshi

doi:10.1253/circj.cj-16-0097

Cited by 24 publications

(26 citation statements)

References 16 publications

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“…Pulmonary endarterectomy (PEA) is a gold standard therapy7, 8; however, PEA for organized thrombus located peripherally in subsegmental pulmonary arteries was less effective and had a high perioperative mortality rate 7, 9. Presently, balloon pulmonary angioplasty (BPA) can be recommended as an established treatment for nonoperable CTEPH patients 10, 11, 12, 13, 14, 15, 16…”

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confidence: 99%

Sequential Hybrid Therapy With Pulmonary Endarterectomy and Additional Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension

Yanaka

Nakayama

Shinke

et al. 2018

JAHA

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BackgroundResidual symptoms after pulmonary endarterectomy (PEA) remain as the clinical issues to be solved. Additional balloon pulmonary angioplasty (BPA) after PEA showed its efficacy with symptoms in a case series, although long‐term spontaneous recovery of exercise ability after PEA was also reported. However, no studies have validated the clinical efficacy of additional BPA by directly comparing PEA with and without BPA. The aim of this study was to retrospectively evaluate the efficacy of additional BPA as a sequential hybrid therapy for chronic thromboembolic pulmonary hypertension after PEA.Methods and ResultsAmong 44 patients with chronic thromboembolic pulmonary hypertension, 20 patients had residual symptoms after PEA. Of those, 10 patients underwent additional BPA (hybrid group) and were compared with the other 10 patients, who were followed up without BPA (PEA group). The period from PEA to additional BPA was 7.3±2.3 months. In hybrid group, mean pulmonary arterial pressure was significantly improved by PEA (40.6±1.8 to 26.9±3.1 mm Hg, P=0.001) and improved further (to 16.7±1.8 mm Hg, P=0.002) with additional BPA, which resulted in remarkable improvement in World Health Organization (WHO) functional class (pre‐ to post‐BPA: class I/II/III/IV, 0/5/4/1 to 7/3/0/0; P<0.001). Compared with the PEA group at follow‐up, the hybrid group achieved better mean pulmonary arterial pressure (18.7±1.7 versus 30.2±3.2 mm Hg, P=0.008), WHO functional class (class I/II/III/IV, 7/3/0/0 versus 0/8/2/0; P=0.001), and 6‐minute walking distance (429±38 versus 319±22 m, P=0.028).ConclusionsA sequential hybrid strategy improved residual symptoms and exercise capacity compared with single‐PEA therapy.

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confidence: 99%

Sequential Hybrid Therapy With Pulmonary Endarterectomy and Additional Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension

Yanaka

Nakayama

Shinke

et al. 2018

JAHA

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“…Iloprost is beneficial in ischemic injury, as well as in other pathological processes, such as infections. It is also an effective agent against pulmonary hypertension (19,20). Alprostadil has similar effects, and its use has been examined in the literature (21,22).…”

Section: Discussionmentioning

confidence: 99%

Comparison between iloprost and alprostadil for protection against ischemia/reperfusion injury in a rat model

2018

Turk J Med Sci

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Background/aim: Alprostadil and iloprost are successful agents used for both pulmonary hypertension and extremity ischemia treatment. Different systemic effects of these agents may change the preferences of clinical usage. Superiority of preventing ischemia/ reperfusion (IR) injury is a criterion for clinical preference of these agents. The present study was designed to compare the protective effects of alprostadil and iloprost in a rat model of IR injury. Materials and methods: Twenty-three male Sprague Dawley rats were used (aged 8-12 weeks, mean weight 230 ± 30 g). They were randomized into 4 groups: Group 1 (iloprost + IR), Group 2 (alprostadil + IR), Group 3 (saline + IR), and Group 4 (control). Under general anesthesia, in all groups except Group 4, the abdominal region was explored and the abdominal aorta was temporarily clamped for 60 min. After the clamp was removed, 120 min of reperfusion was applied. In Group 4, the rats were placed under general anesthesia and abdominal exploration was performed without the IR procedure. For all rats, body temperature was kept at 36 °C with a heater pad through the whole procedure. The rats were euthanized under general anesthesia to remove the kidneys and lungs for study. Histopathological and biochemical analyses were conducted with kidney and lung tissues. Histopathological scoring was done by analyzing cellular damage at tissue level. Malondialdehyde (MDA), superoxide dismutase, and glutathione levels were studied for biochemical analysis. Results: Histopathologic analysis showed that, as compared with alprostadil, iloprost provided a significantly higher level of renal protection against IR injury (P < 0.01). Renal tissue levels of MDA were significantly lower in the alprostadil group as compared to Group 3 (P < 0.05). Conclusion: Alprostadil and iloprost seem to provide protection against IR injury, with iloprost being more protective in renal tissue. Alprostadil is more effective than iloprost in protecting lung tissue against IR injury.

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“…When administered in adult patients with pulmonary arterial hypertension in an open‐label study, the most common adverse events were headache and cough (table ). One patient experienced hypotension . The use of aerosolised iloprost has shown a subsequent rapid tolerance development to the vasodilatory effect .…”

Section: Therapy Of Pphnmentioning

confidence: 99%

Current and Future Treatments for Persistent Pulmonary Hypertension in the Newborn

Maibom

Hedegaard

Simonsen

et al. 2018

Basic Clin Pharma Tox

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Persistent pulmonary hypertension in newborn (PPHN) is a serious and possibly fatal syndrome characterized by sustained foetal elevation of pulmonary vascular resistance at birth. PPHN may manifest secondary to other conditions as meconium aspiration syndrome, infection and congenital diaphragmatic hernia. This MiniReview provides the reader with an overview of current and future treatment options for patients with PPHN without congenital diaphragmatic hernia. The study is based on systematic searches in the databases PubMed and Cochrane Library and registered studies on Clinicaltrials.gov investigating PPHN. Inhaled nitric oxide (iNO) is well documented for treatment of PPHN, but 30% fail to respond to iNO. Other current treatment options could be sildenafil, milrinone, prostaglandin analogues and bosentan. There are several ongoing trials with sildenafil, but evidence is lacking for the other treatments and/or for the combination with iNO. Currently, there is no evidence for effect in PPHN of other treatments, for example tadalafil, macitentan, ambrisentan, riociguat and selexipag used for pulmonary arterial hypertension in adults. Experimental studies in animal models for PPHN suggest effect of a series of approaches including recombinant human superoxide dismutase, L-citrulline, Rho-kinase inhibitors and peroxisome proliferator-activated receptor-γ agonists. We conclude that iNO is the most investigated and the only approved pulmonary vasodilator for infants with PPHN. In the iNO non-responders, sildenafil currently seems to be the best alternative either alone or in combination with iNO. Systematic and larger clinical studies are required for testing the other potential treatments of PPHN.

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Efficacy and Safety of Inhaled Iloprost in Japanese Patients With Pulmonary Arterial Hypertension　– Insights From the IBUKI and AIR Studies –

Cited by 24 publications

References 16 publications

Sequential Hybrid Therapy With Pulmonary Endarterectomy and Additional Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension

Sequential Hybrid Therapy With Pulmonary Endarterectomy and Additional Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension

Comparison between iloprost and alprostadil for protection against ischemia/reperfusion injury in a rat model

Current and Future Treatments for Persistent Pulmonary Hypertension in the Newborn

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Efficacy and Safety of Inhaled Iloprost in Japanese Patients With Pulmonary Arterial Hypertension – Insights From the IBUKI and AIR Studies –

Cited by 24 publications

References 16 publications

Sequential Hybrid Therapy With Pulmonary Endarterectomy and Additional Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension

Sequential Hybrid Therapy With Pulmonary Endarterectomy and Additional Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension

Comparison between iloprost and alprostadil for protection against ischemia/reperfusion injury in a rat model

Current and Future Treatments for Persistent Pulmonary Hypertension in the Newborn

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Efficacy and Safety of Inhaled Iloprost in Japanese Patients With Pulmonary Arterial Hypertension　– Insights From the IBUKI and AIR Studies –