Oral sildenafil as long-term adjunct therapy to inhaled iloprost in severe pulmonary arterial hypertension

We sought to investigate the impact of adjunct sildenafil on exercise capacity and hemodynamic parameters in patients with pulmonary arterial hypertension (PAH) who fulfilled predefined criteria of deterioration despite ongoing treatment with inhaled iloprost. Inhaled iloprost is an effective therap...

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Published in:Journal of the American College of Cardiology 2003-07, Vol.42 (1), p.158-164
Main Authors: Ghofrani, Hossein A, Rose, Frank, Schermuly, Ralph T, Olschewski, Horst, Wiedemann, Ralph, Kreckel, André, Weissmann, Norbert, Ghofrani, Stefanie, Enke, Beate, Seeger, Werner, Grimminger, Friedrich
Format: Article
Language:English
Subjects:
3',5'-Cyclic-GMP Phosphodiesterases - therapeutic use
Biological and medical sciences
Cardiology
Cardiovascular system
Drug therapy
Drug Therapy, Combination
Enzymes
Female
Heart
Hemodynamics - drug effects
Humans
Hypertension, Pulmonary - drug therapy
Hypertension, Pulmonary - physiopathology
Iloprost - therapeutic use
Male
Medical sciences
Middle Aged
Nitric oxide
Pharmacology. Drug treatments
Piperazines - pharmacology
Piperazines - therapeutic use
Pulmonary arteries
Pulmonary hypertension
Purines
Sildenafil Citrate
Studies
Sulfones
Vascular Resistance - drug effects
Vasodilator Agents - pharmacology
Vasodilator Agents - therapeutic use
Vasodilator agents. Cerebral vasodilators
Veins & arteries
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Summary:We sought to investigate the impact of adjunct sildenafil on exercise capacity and hemodynamic parameters in patients with pulmonary arterial hypertension (PAH) who fulfilled predefined criteria of deterioration despite ongoing treatment with inhaled iloprost. Inhaled iloprost is an effective therapy in PAH. The phosphodiesterase-5 inhibitor sildenafil exerts pulmonary vasodilation and may amplify prostanoid efficacy. Of 73 PAH patients receiving long-term inhaled iloprost treatment, 14 fulfilled criteria of deterioration unresponsive to conventional treatment. These patients received adjunct oral sildenafil over a period of nine to 12 months, leaving the inhalative iloprost regimen unchanged. Before iloprost therapy, the baseline 6-min walking distance was 217 ± 31 m (mean ± SEM), with an improvement to 305 ± 28 m within the first three months of iloprost treatment and a subsequent decline to 256 ± 30 m after 18 ± 4 months. Adjunct therapy with sildenafil reversed the deterioration and increased the 6-min walk distance to 346 ± 26 m (p = 0.002, Wilcoxon test) at three months of combined therapy, with a sustained efficacy up to 12 months (349 ± 32 m, p = 0.002). The distribution of New York Heart Association functional classes (IV/III/II) improved from September 9, 2000, before sildenafil, to January 8, 2003, after nine to 12 months with sildenafil. All hemodynamic variables changed favorably: pulmonary vascular resistance decreased from 2,494 ± 256 before sildenafil to 1,950 ± 128 dynes·s·cm−5·m2after three months of adjunct sildenafil (p = 0.036). Two patients died of severe pneumonia during the period of combined therapy. No further serious adverse events occurred. In patients with severe PAH deteriorating despite ongoing prostanoid treatment, long-term adjunct oral sildenafil improves exercise capacity and pulmonary hemodynamics. A combination of prostanoids and sildenafil is an appealing concept for future treatment of pulmonary hypertension.
ISSN:0735-1097
1558-3597
DOI:10.1016/S0735-1097(03)00555-2