-
[show abstract]
[hide abstract]
ABSTRACT: Portopulmonary hypertension (POPH) is regarded as a subtype of pulmonary arterial hypertension (PAH); however, established PAH therapies have not been evaluated for this condition. The current authors treated 14 patients (four male, 10 female; mean (range) age 55 (39-75) yrs) with moderate (n = 1) or severe (n = 13) POPH caused by alcoholic liver disease (n = 7), chronic viral hepatitis (n = 3), autoimmune hepatitis (n = 3), and hepatic manifestation of hereditary haemorrhagic teleangiectasia (n = 1) with oral sildenafil. Eight patients were newly started on pulmonary vasoactive treatment, while six patients were already on treatment with inhaled prostanoids (iloprost, n = 5; treprostinil, n = 1). During treatment with sildenafil, mean +/- sd 6-min walk distance increased from 312 +/- 111 m to 397 +/- 99 m after 3 months, and 407 +/- 97 m after 12 months. Mean +/- sd pro-brain natriuretic peptide levels decreased from 582 +/- 315 ng x mL(-1) to 230 +/- 278 ng x mL(-1), and to 189 +/- 274 ng x mL(-1) after 3 and 12 months, respectively. Two patients died after 1 and 2 months from liver failure and cardiac failure, respectively. There was a similar response to sildenafil treatment after 3 and 12 months in patients on monotherapy and those on combination therapy. In conclusion, sildenafil might be effective in monotherapy and in combination therapy with inhaled prostanoids in portopulmonary hypertension, leading to significant improvement by 3 months and sustained response over 12 months.
European Respiratory Journal 10/2006; 28(3):563-7. · 5.89 Impact Factor
-
H Olschewski,
A Ghofrani,
B Enke,
F Reichenberger,
R Voswinckel, A Kreckel,
S Ghofrani,
R Wiedemann,
R Schulz,
F Grimminger,
W Seeger
[show abstract]
[hide abstract]
ABSTRACT: New drugs for pulmonary arterial hypertension have shown efficacy in randomized controlled trials. Endothelin receptor antagonists (ERA) and prostanoids are most important for clinical practice. Bosentan represents the first approved orally active therapy for PAH. Besides its hepatotoxicity it is mostly well tolerated. The first approved prostanoid, epoprostenol, is currently first choice only for decompensated right heart failure in PAH. It has to be delivered continuously intravenously and is prone to complications, side effects and very high costs. Alternatively, subcutaneous treprostinil can be applied. It is less risky and expensive but may cause local pain at the infusion site. Inhaled iloprost combines the features of a prostanoid with pulmonary and intrapulmonary selectivity. Alternatively, iloprost is being used as continuous intravenous infusion. The phosphodiesterase-5 inhibitor sildenafil was effective in two randomized controlled trials but has not been approved for PAH therapy.
Der Internist 04/2005; 46(3):341-9. · 0.30 Impact Factor
-
H. Olschewski,
A. Ghofrani,
B. Enke,
F. Reichenberger,
R. Voswinckel, A. Kreckel,
S. Ghofrani,
R. Wiedemann,
R. Schulz,
F. Grimminger,
W. Seeger
[show abstract]
[hide abstract]
ABSTRACT: Neue Medikamente zur Therapie der pulmonal arteriellen Hypertonie (PAH) haben ihre Wirksamkeit in randomisierten kontrollierten Studien belegt. Die grte praktische Bedeutung haben hier Endothelinrezeptorantagonisten und Prostanoide. Bosentan ist die erste zugelassene oral verfgbare Therapie der PAH. Das Medikament ist abgesehen von einer seltenen Hepatotoxizitt meist gut vertrglich. Das zuerst zugelassene Prostanoid, Epoprostenol, ist nur noch fr die dekompensierte Rechtsherzinsuffizienz das Mittel der ersten Wahl, da es nur kontinuierlich intravens appliziert werden kann und durch Komplikationen, Nebenwirkungen und sehr hohe Kosten belastet ist. Als Alternative steht die subkutane Dauerinfusion des weniger risikoreichen und preiswerteren Treprostinil zur Verfgung. Dieses Prostanoid hat eine lngere Halbwertszeit, verursacht aber vielfach Schmerzen an der Injektionsstelle. Inhalatives Iloprost verbindet die Vorzge des Prostanoids mit einer (intra)pulmonal selektiven Wirkung. Iloprost wird alternativ auch als Dauerinfusion angewendet. Der Phosphodiesterase-5-Inhibitor Sildenafil zeigte eine signifikante Wirksamkeit in 2 randomisierten kontrollierten Studien, steht aber noch vor der Zulassung zur Therapie der PAH.New drugs for pulmonary arterial hypertension have shown efficacy in randomized controlled trials. Endothelin receptor antagonists (ERA) and prostanoids are most important for clinical practice. Bosentan represents the first approved orally active therapy for PAH. Besides its hepatotoxicity it is mostly well tolerated. The first approved prostanoid, epoprostenol, is currently first choice only for decompensated right heart failure in PAH. It has to be delivered continuously intravenously and is prone to complications, side effects and very high costs. Alternatively, subcutaneous treprostinil can be applied. It is less risky and expensive but may cause local pain at the infusion site. Inhaled iloprost combines the features of a prostanoid with pulmonary and intrapulmonary selectivity. Alternatively, iloprost is being used as continuous intravenous infusion. The phosphodiesterase-5 inhibitor sildenafil was effective in two randomized controlled trials but has not been approved for PAH therapy.
Der Internist 02/2005; 46(3):341-349. · 0.30 Impact Factor
-
R. Voswinckel,
F Reichenberger,
B Enke, A Kreckel,
S Krick,
H Gall,
R. T. Schermuly,
F Grimminger,
L J Rubin,
H Olschewski,
W Seeger,
H A Ghofrani
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Inhaled treprostinil was recently developed for the treatment of pulmonary arterial hypertension (PAH). We investigated the safety and acute haemodynamic effects of the combination oral sildenafil and inhaled treprostinil in an open label study in patients with precapillary pulmonary hypertension. METHODS AND PATIENTS: Inhaled nitric oxide (20ppm; n=50), sildenafil (50mg; n=50) and inhaled treprostinil (15microg; n=25 or 30microg; n=25) were applied in subsequent order during right heart catheter investigation to consecutive patients with pulmonary arterial hypertension (PAH; n=28), non-operable chronic thromboembolic pulmonary hypertension (CTEPH; n=17) and pulmonary fibrosis associated pulmonary hypertension (n=5). RESULTS: Inhaled nitric oxide reduced pulmonary vascular resistance (PVR) to 87.3+/-5.1% of baseline values, reduced mean pulmonary arterial pressure (PAP) to 89.7+/-3.5% and increased cardiac output (CO) to 102.4+/-2.9%. Sildenafil reduced PVR to 80.1+/-5.0%, mPAP to 86.5+/-2.9% and increased CO to 103.8+/-3.2%. Treprostinil, inhaled 1h after sildenafil, reduced PVR to 66.3+/-3.8%, mPAP to 77.8+/-3.3%, and increased CO to 107.1+/-3.3% (mean+/-95% confidence interval). Subgroup analysis showed similar acute haemodynamic effects in PAH and CTEPH patients. Ventilation/perfusion distribution measurement in six patients with pre-existing gas exchange limitations was not changed by sildenafil and treprostinil. Relevant side effects were not observed. CONCLUSION: The combination of sildenafil and inhaled treprostinil was well tolerated and induced additive, pulmonary selective vasodilatation in pulmonary hypertension patients. This could be of relevance also for long-term treatment of PAH and CTEPH patients.
Pulm Pharmacol Ther, v.21, 824-832 (2008).
