Differences in hemodynamic and oxygenation responses to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension: a randomized prospective study.
OBJECTIVE
We sought to compare the short-term impact 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.
Ghofrani
Hossein A
HA
Department of Internal Medicine, University Hospital Giessen, Giessen, Germany.
Voswinckel
Robert
R
Reichenberger
Frank
F
Olschewski
Horst
H
Haredza
Peter
P
Karadaş
Burcu
B
Schermuly
Ralph T
RT
Weissmann
Norbert
N
Seeger
Werner
W
Grimminger
Friedrich
F
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002243:Carbolines / Q000494:pharmacology; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood*; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology; D011446:Prospective Studies; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D000068581:Tadalafil; D016896:Treatment Outcome; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D002243:Carbolines; D004791:Enzyme Inhibitors; D007093:Imidazoles; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014227:Triazines; D014665:Vasodilator Agents; D000069058:Vardenafil Dihydrochloride; D000068581:Tadalafil; D000068677:Sildenafil Citrate; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human; D010100:Oxygen