PULMONARY HYPERTENSION
Differences in hemodynamic and oxygenation responses to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension
A randomized prospective study
Hossein A. Ghofrani, MD,
Robert Voswinckel, MD,
Frank Reichenberger, MD,
Horst Olschewski, MD,
Peter Haredza,
Burcu Karada ,
Ralph T. Schermuly, PhD,
Norbert Weissmann, PhD,
Werner Seeger, MD and
Friedrich Grimminger, MD*
Department of Internal Medicine, University Hospital Giessen, Giessen, Germany
Manuscript received April 21, 2004;
revised manuscript received May 26, 2004,
accepted June 7, 2004.
* Reprint requests and correspondence: Dr. Friedrich Grimminger, Department of Internal Medicine, University Hospital Giessen, Klinikstrasse 36, 35392 Giessen, Germany
(Email: friedrich.grimminger{at}innere.med.uni-giessen.de).
OBJECTIVES: We sought to compare the short-termimpact of three different phosphodiesterase-5 (PDE5) inhibitors on pulmonary and systemic hemodynamics and gas exchange parameters in patients with pulmonary arterial hypertension (PAH).
BACKGROUND: The PDE5 inhibitor sildenafil has been reported to cause pulmonary vasodilation in patients with PAH. Vardenafil and tadalafil are new PDE5 inhibitors, recently being approved for the treatment of erectile dysfunction.
METHODS: Sixty consecutive PAH patients (New York Heart Association functional class II to IV) who underwent right heart catheterization received short-term nitric oxide (NO) inhalation and were subsequently assigned to oral intake of 50 mg sildenafil (n = 19), 10 mg (n = 7) or 20 mg (n = 9) vardenafil, or 20 mg (n = 9), 40 mg (n = 8), or 60 mg (n = 8) tadalafil. Hemodynamics and changes in oxygenation were assessed over a subsequent 120-min observation period.
RESULTS: All three PDE5 inhibitors caused significant pulmonary vasorelaxation, with maximum effects being obtained after 40 to 45 min (vardenafil), 60 min (sildenafil), and 75 to 90 min (tadalafil). Sildenafil and tadalafil, but not vardenafil, caused a significant reduction in the pulmonary to systemic vascular resistance ratio. Significant improvement in arterial oxygenation (equally to NO inhalation) was only noted with sildenafil.
CONCLUSIONS: In PAH patients, the three PDE5 inhibitors differ markedly in their kinetics of pulmonary vasorelaxation (most rapid effect by vardenafil), their selectivity for the pulmonary circulation (sildenafil and tadalafil, but not vardenafil), and their impact on arterial oxygenation (improvement with sildenafil only). Careful evaluation of each new PDE5 inhibitor, when being considered for PAH treatment, has to be undertaken, despite common classification as PDE5 inhibitors.
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Abbreviations and Acronyms
| | cGMP = cyclic guanosine monophosphate | | CI = confidence interval | | mPAP = mean pulmonary arterial pressure | | NO = nitric oxide | | NYHA = New York Heart Association | | PAH = pulmonary arterial hypertension | | PDE = phosphodiesterase | | PVRI = pulmonary vascular resistance index | | SVRI = systemic vascular resistance index |
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